Methods and Devices for Controlling Biologic Microenvironments

ABSTRACT

A microenvironment of a biological body is controlled, and more particularly, is measured, changed, and monitored with respect to temperature, pH level, moisture and other tissue parameters of a region of the body while, optionally, administering a therapeutic agent to that region.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication 60/828,084 to the same inventor, filed Oct. 4, 2006,entitled METHODS AND DEVICES FOR CONTROLLING BIOLOGIC MICROENVIRONMENTS,the entire contents of which are incorporated herein by reference.

FIELD OF THE INVENTION

The invention relates to controlling a microenvironment of a biologicalbody, and more particularly, to measuring, changing, and monitoring thetemperature, pH level, moisture and other tissue parameters of a regionof the body while, optionally, administering a therapeutic agent to thatregion.

BACKGROUND OF THE INVENTION

The human body and bodies of other mammals naturally maintain a certainlevel of temperature, pH, humidity, etc. The normal temperature of thehuman body is, for example, 98.6 degrees Fahrenheit. This temperaturelevel, however, is not consistent throughout the entire body. Differentbody regions may be higher or lower than 98.6 degrees. Acidity levelsalso vary. Certain body parts, such as the stomach or intestines mayhave a different pH level than the brain or heart. Also, temperature andacidity levels vary in the body throughout the day, depending on thelevel of activity of a particular person. A person sleeping will havedifferent pH levels than the same person exercising.

Other factors that determine the microenvironment of the body isdisease, damage, and injury to tissue. The body may somewhat fluctuatethe microclimate of tissue during healing, to fight infection, and toresist or kill a foreign object. However, augmenting the body's abilityto control the microenvironment enhances tissue healing. Some patentdocuments disclose various methods, devices, and reasons for controllingthe body's temperature, pH level, moisture, and other microclimateparameters.

U.S. Pat. No. 7,056,318 entitled “Temperature Controlled Heating Deviceand Method to Heat a Selected Area of a Biological Body” discloses aheating device and method for controlling a temperature in a selectedarea of a body part to obtain a temperature effect within the selectedarea for therapeutic or medical purposes. It includes temperaturegenerating means to generate a temperature in the selected area. It alsoincludes temperature detecting means to detect the generated temperaturefrom the selected area. It further includes temperature controllingmeans to control the temperature generating means to maintain thegenerated temperature within a range of a desired temperature. Thedevice and method prevent irreversibly damaging or overheating theselected area or the tissue surrounding the selected area. It isadvantageous to applications where there is a need to accurately controlthe temperature in a selected area in a biological body, for instance,to activate or evaporate a temperature sensitive agent in the selectedarea.

U.S. Pat. No. 7,004,961 entitled “Medical Device and Method forTemperature Control and Treatment of the Brain and Spinal Cord”discloses a medical device having a thermostat for temperaturemeasurement, irrigation/aspiration ports for fluid exchange andapplication of therapeutic modalities, a pressure manometer for pressuremeasurement, and an external system for control of temperature,pressure, and flow rate. When applied to the central nervous system(CNS), this device can be used in hypothermia or hyperthermiaapplications, the exchange of cerebral spinal fluid (CSF), theapplication of treatment modalities, and the insertion of aventriculostomy or ventriculostomy-like unit. When applied to spinalcord applications, this device can provide temperature control and amethod for application of treatment modalities by using a venting deviceplaced in the space surrounding the spinal cord, a device with similarinstrumentation to measure temperature and pressure.

U.S. Pat. No. 7,004,933 entitled “Ultrasound Enhancement of PercutaneousDrug Absorption” discloses a system for enhancing and improving thetranscutaneous or transdermal delivery of topical chemicals or drugs. Adisposable container contains a substantially sterile unit dose of anactive agent adapted for a single use in a medical treatment. The unitdose is formulated to enhance transport of the active agent throughmammalian skin when the active agent is applied to the skin and the skinis exposed to light and/or ultrasound defined by at least one specificparameter.

U.S. Pat. No. 6,961,620 entitled “Apparatus and Methods for AssistingAblation of Tissue Using Magnetic Beads” discloses a system for treatingtissue includes a source of conductive and/or magnetic beads, a firstmember, e.g., a catheter or cannula, coupled to the source of magneticbeads, and a second member, e.g., a catheter or cannula, carrying amagnet on its distal end. The system is used for ablating or otherwisetreating tissue within a target tissue region including a blood vesselcontacting or passing therethrough. Magnetic beads are introduced intothe target tissue region, e.g., using the first member, and a magneticfield is generated within the target tissue region, e.g., using thesecond member, to cause the magnetic beads to migrate towards a wall ofthe vessel. Energy is delivered into the target tissue region, e.g., toheat tissue therein, and the magnetic beads may attenuate or enhancetreatment of tissue adjacent to the vessel.

U.S. Pat. No. 6,600,941 entitled “Systems and Methods of pH TissueMonitoring” discloses the use of pH measurements of tissue as a systemfor controlling diagnostic and/or surgical procedures. The inventionalso relates to an apparatus used to perform tissue pH measurements.Real time tissue pH measurements can be used as a method to determineischemic segments of the tissue and provide the user with courses ofconduct during and after a surgical procedure. When ischemia is found tobe present in a tissue, a user can affect an optimal delivery ofpreservation fluids to the site of interest and/or effect a change inthe conduct of the procedure to raise the pH of the site.

U.S. Patent Publication No. 2005/0267565 entitled “Biodegradable MedicalImplant with Encapsulated Buffering Agent” discloses a medical devicefor placement at a site in a patient's body and for controlling pHlevels at the site in the patient's body includes one or more structuralcomponents made of a first biodegradable and/or bioabsorbable materialor, alternatively, one or more structural components having a coatingthereon made of a first biodegradable and/or bioabsorbable material. Thedevice also includes a buffering agent and at least one secondbiodegradable and/or bioabsorbable material on or in the one or morestructural components, or alternatively, on or in the coating on the oneor more structural components. The at least one second biodegradableand/or bioabsorbable material encapsulates the buffering agent and thebuffering agent is dispersed from the at least one second biodegradableand/or bioabsorbable material in response to hydrolysis of the firstbiodegradable and/or bioabsorbable material. Additionally, the devicecan include a drug that is either also encapsulated by the at least onesecond biodegradable and/or bioabsorbable material or is included withthe first biodegradable and/or bioabsorbable material

There exists a need for apparatus and methods for controlling thebiologic microenvironment of a body region by measuring, changing, andmonitoring the temperature, pH level, moisture level, and othermicroenvironment parameters and simultaneously delivering apharmaceutical/therapeutic agent.

SUMMARY OF THE INVENTION

The present invention relates to devices and methods for controllingmicroenvironments in living organisms. The microenvironment (ormicroclimate) of a region of the body is defined as thosecharacteristics which create the conditions necessary for cells tofunction. Such characteristics may include temperature, pH level,moisture, humidity, oxygen tension, oxygenase, carbon dioxide tension,rate of blood flow, nutrient-content, osmolarity, pressure, vascularpermeability, electrical charge, and the presence of pharmaceuticalagents. Some of these characteristics, like temperature, may benaturally controlled by the body. However, as a result of disease, age,injury, or surgery, the body may require augmentation for controllingthe microenvironment of a body region. The present invention providesfor measuring, changing, and monitoring microenvironment parameters.Through the use of sensors, implanted or externally positioned, theparameters may be measured. A physician or sensors/microprocessordetermines whether the measured levels are appropriate for the selectedbody region. If not, the levels may be adjusted. Continuous monitoringof the microenvironment creates a feedback loop so that themicroenvironment characteristics may be selectively controlled, manuallyor automatically.

Optimizing the microenvironment with the devices and methods of thepresent invention may be used to enhance or improve the effect oftherapeutic/pharmaceutical agents, improve the outcome of a surgicalprocedure or intervention, enhance the results of a surgical implant,optimize cell or tissue ingrowth when using cell therapy or genetherapy, and other advantages which are described in relation to theexemplary embodiments. Controlling the microenvironment with thismultimodal approach may be performed preoperatively, during surgicaltreatment, and postoperatively.

Other benefits for controlling the microenvironment include effectingcell receptors, effecting hormone release, effecting tissue healing,effecting the ability of bacteria to multiple or reduce, effecting virusactivity, stimulating white blood cells enzyme release, stimulatingwhite blood cell phagocytosis or migration, and managing pain.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the present invention, and theattendant advantages and features thereof, will be more readilyunderstood by reference to the following detailed description whenconsidered in conjunction with the accompanying drawings wherein:

FIG. 1 illustrates an endoscope positioned in a body region forcontrolling the microclimate thereof;

FIG. 2 shows a multi-lumen catheter inserted in a body region and havingan endoscope and sensors extending therefrom;

FIG. 3 illustrates an intramedullary rod designed for controlling themicroenvironment of a bone fracture;

FIG. 4 is a cross sectional view of a fastener configured forcontrolling the microenvironment;

FIG. 5 shows a bone plate designed for controlling the microenvironmentof a bone fracture;

FIG. 6 illustrates a spinal implant constructed to control themicroenvironment of a spinal region;

FIG. 7 is a perspective view knee replacement components designed forcontrolling the microenvironment of a knee joint;

FIGS. 8A and 8B show an acetabular implant configured to control themicroenvironment of a joint area;

FIG. 9 is a top view of a mesh sheet having integral,microenvironment-controlling means;

FIG. 10 is a cross sectional view of a tubular mesh constructed forcontrolling the microenvironment of a vessel;

FIG. 11 is a partial cut away view of an implant designed to control themicroenvironment of a blood vessel;

FIG. 12 shows apparatus for controlling the microenvironment of a jointduring joint replacement surgery;

FIG. 13 illustrates devices connected with a stomach for controlling themicroenvironment thereof and thereby controlling the appetite of theperson;

FIG. 14 is a cross sectional view of a device for correcting visiondefects of an eye;

FIG. 15 shows a tissue patch having microenvironment-controllingdevices;

FIG. 16 illustrates a device for controlling the microenvironment ofskin;

FIGS. 17A and 17B show an apparatus for iontophoretic treatment oftissue;

FIG. 18 is a perspective view of a hat for controlling microenvironmentsof the head;

FIG. 19 is a perspective view of a collar for controllingmicroenvironments of the neck;

FIG. 20 is a front view of a suit for controlling one or moremicroenvironments of the human body;

FIG. 21 shows a glove for controlling microenvironments of the hand;

FIG. 22 shows a filter of the present invention having integratedmicroenvironment-controlling means;

FIG. 23 illustrates another filter having an external controller;

FIG. 24 illustrates an aerosol drug delivery system of the presentinvention;

FIG. 25 shows a compressed gas drug delivery system;

FIG. 26 is a cross sectional view of a distraction drug delivery system;

FIG. 27 is a cross sectional view of another distracting drug deliveringsystem of the present invention;

FIGS. 28A and 28B illustrate a omni-directional drug dispersal system;

FIG. 29A shows a partially implanted drug delivery apparatus of thepresent invention;

FIG. 29B illustrates a fully implanted, externally controlled drugdelivery device;

FIG. 30A is a top view of a generator joint; and

FIG. 30B is a side view of the generator joint of FIG. 30A.

FIG. 31 illustrates a device in accordance with the invention forcontrolling a microclimate;

FIG. 32 is an alternative to the device of FIG. 31, having a groundedcase;

FIG. 33 illustrates a waveform illustrating a change in magneticwaveform operative to generate heat;

FIG. 34 illustrates a circuit to create and control a sinusoidal signal;

FIG. 35 illustrates a circuit for monitoring temperature;

FIG. 36 illustrates a control circuit for magnet control, with heartrate input, and controls;

FIG. 37 illustrates heart monitor and control signals;

FIG. 38 illustrates a radio frequency energy delivery circuit;

FIG. 39 illustrates an ultrasonic generator circuit; and

FIG. 40 illustrates a resistive heater circuit.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to devices and methods for controllingmicroenvironments in living organisms. Characteristics of themicroenvironment that may be controlled include temperature, pH,moisture, humidity, oxygen-content, oxygenase, carbon dioxide-content,rate of blood flow, nutrient-content, osmolarity, pressure, vascularpermeability, electrical charge, and the presence of pharmaceutical ortherapeutic agents. These characteristics may be measured, changed, andmonitored automatically and/or selectively by a physician to obtain theoptimal environment for a particular body region. Continuous monitoringof the microenvironment creates a feedback loop so that themicroenvironment characteristics may be continuously controlled.

Implanted Systems

Referring to FIG. 1, a surgical instrument is shown positioned in aregion of a living body. The region naturally includes tissue whichrequires certain levels of environmental parameters for proper function.These parameters may include temperature, pH level, moisture, humidity,oxygen tension, carbon dioxide tension, rate of blood flow,nutrient-content, the presence of pharmaceutical agents, etc. Throughthe use of various surgical instruments, these parameters may bemeasured, changed, and monitored.

An endoscope 10, shown in FIG. 1, includes a viewing port 12 such as acamera lens, a sensor 14, a delivery port 16, and a heating/cooling unit18. Cooling units may include a Peltier cooler, optionally includingmeans to dissipate or redirect heat generated, including a heat sink,and or a liquid circulation system. The viewing port 12 allows thephysician to precisely insert the endoscope 10 in the region 20 andprovides visualization of the microenvironment region. The sensor 14 isdesigned to respond to physical stimuli and transmit resulting impulsesfor interpretation, recording, or operating control. A display screen(not shown) may be positioned outside the living body and in view of thephysician. The screen and related electronic components process anddisplay the sensor readings. The sensor 14 may be a temperature sensor,pH level sensor, moisture sensor, oxygen sensor, carbon dioxide sensor,or any other sensor to measure microenvironment characteristics. Thedelivery port 16 is in fluid communication with a lumen within theendoscope and a reservoir (not shown). The delivery port and reservoir16 are configured for delivering a liquid, gas, gel, powder, and/orsolid to affect the microenvironment of the region 20.

Therapeutic substances to control the microenvironment may includeantibiotics, hydroxypatite, anti-inflammatory agents, steroids,antibiotics, analgesic agents, chemotherapeutic agents, bonemorphogenetic protein, demineralized bone matrix, collagen, growthfactors, autogenetic bone marrow, progenitor cells, calcium sulfate,immu-suppressants, fibrin, osteoinductive materials, apatitecompositions, fetal cells, stem cells, enzymes, proteins, hormones,germicides, non-proliferative agents, anti-coagulants, anti-plateletagents, Tyrosine Kinase inhibitors, anti-infective agents, anti-tumoragents, anti-leukemic agents, and combinations thereof

The heating/cooling unit 18 of the endoscope permits the physician toadjust the temperature of the microenvironment. The unit 18 may be aresistive heater, an ultrasonic heater, IR heater, RF heater, microwaveheater, or a convection/conduction cooling device. By controlling thetemperature of the region, other parameters, such as pH, blood flowrate, etc., may be controlled as a result. For example, raising thetemperature of the microenvironment region, the pH level may beincreased.

In FIG. 2, another embodiment for controlling the microenvironment isshown. A multi-lumen catheter or cannula 22 includes an endoscopechannel 24, a surgical instrument channel 26, and a plurality ofmicroenvironment-control channels 28. The endoscope channel 24 isconfigured to receive an endoscope 10 like that of FIG. 1. Theinstrument channel 26 provides access for a physician to insert medicalinstruments into the region 20 of the body. The microenvironment-controlchannels 28 are configured for insertion of sensors 14 andheating/cooling units 18 into the microenvironment region 20. Thesensors 14 and heating/cooling units 18 are of the types previouslydescribed. The microenvironment-control channels 28 may also beconfigured for delivery of gases, liquids, gels, and solids. Therapeuticagents may be delivered via the microenvironment-control channels.

To control the microenvironment of the region, a physician may utilizethe devices of FIGS. 1 and 2 as follows. A small incision may be made inthe skin of the patient, and soft tissue may be distracted with a trocaror guidewire to create a path to the region 20 requiringmicroenvironment adjustment. The cannula may be inserted through theincision and in the path. For a region accessible through an orifice ofthe body, the cannula may be positioned through the orifice withoutneeding to make an incision in the skin. With the cannula positioned inthe body, the endoscope 10 may be inserted in the endoscope channel ofthe cannula. The endoscope 10 may be steered by the physician to locateand analyze the desired body region. A sensor 14 and/or heating/coolingunit 18 may be inserted into the microenvironment-control channels 28 ofthe cannula.

As shown in FIG. 2, a sensor 14 is deployed from the cannula 22 andpositioned against tissue in the body region 20. Also, a heating/coolingunit 18 is deployed from the cannula 22 and positioned against thetissue. A connection member 30 such as a wire or plastic rod carries thesensor 14 and/or heating/cooling unit 18. Electrical or optical wiringmay be located within or adjacent the connection member 30 to carrysignals between a control unit (not shown) and the sensor 14 andheating/cooling unit 18. Based on the measured microenvironmentparameters of the region, the physician may selectively change one ormore of the parameters and/or administer one or more therapeutic agentsto the region.

The surgical instruments of FIGS. 1 and 2 may be utilized with minimallyinvasive surgery techniques disclosed in U.S. Pat. Nos. 6,702,821;6,770,078; and 7,104,996. These patent documents disclose, inter alia,apparatus and methods for minimally invasive medical procedures. U.S.Pat. Nos. 6,702,821; 6,770,078; and 7,104,996 are hereby incorporated byreference.

Referring now to FIG. 3, another apparatus for controlling themicroenvironment of a body region is shown. In FIGS. 1 and 2, themicroenvironment of soft tissue was manipulated, while in FIG. 3 themicroenvironment of hard tissue, such as bone 32, is controlled. Thebone 32 has a fracture 34 or other injury therein. The implant of FIG. 3is an intramedullary rod 36 which stabilizes the fractured bone. The IMrod 36 may be made of metallic, ceramic, or polymeric material. The IMrod 36 may include thermoplastic material which is formable with theapplication of heat. Patent documents which further describe suchthermoplastic implants include U.S. patent application Ser. No.11/416,618 filed May 3, 2006 and U.S. Provisional Patent ApplicationNos. 60/765,857 filed Feb. 7, 2006; 60/784,186 filed Mar. 21, 2006; and60/810,080 filed Jun. 1, 2006, all of which are hereby incorporated byreference.

The IM rod 36 of the present invention includes sensors 14,heating/cooling units 18, and an electronic controller 38. The sensors14 may be temperature sensors, pH sensors, moisture sensors, oxygensensors, carbon dioxide sensors, or other sensors to measuremicroenvironment characteristics. The heating/cooling units 18 may beresistive heaters, ultrasonic heaters, IR heaters, RF heaters, microwaveheaters, or convection/conduction cooling devices. Both the sensors 14and heating/cooling units 18 may be controlled by the electroniccontroller 38, either automatically based on predetermined measurementsor manually via remote control. Manual control of the implantedelectronic processor may be achieved through IR, RF, or microwave energyor through an implanted wire.

The IM rod 36 also includes delivery ports 16, a reservoir 40, and areservoir controller 42. Each delivery port 16 is in fluid communicationwith the reservoir 40 by way of piping 44. The delivery ports 16 andreservoir 40 are configured for delivering a liquid, gas, gel, and/orsolid to affect the microenvironment of the region. The substanceadministered through the delivery ports may be any of the agents orsubstances disclosed herein. The reservoir controller 42 manipulates therelease rate and release period of the substance(s) in the reservoir 40.The reservoir controller 42 and electronic processor 38 may be linkedtogether to function as a single system. That is, the reservoircontroller and electronic processor work together to control themicroenvironment of the body region. Alternatively, the reservoircontroller and electronic processor may be physically integrated intoone assembly.

The microenvironment of a fracture 34 of a bone 32 may be controlledwith the IM rod 36 of FIG. 3 by the following method. The medullarycanal of the fractured bone 32 is cleared out and formed to receive theIM rod 36. The rod 36 is inserted into the medullary canal such that thesensors 14, heating/cooling units 18, and delivery ports 16 are adjacentthe fracture 34. If the bone includes multiple fractures, then thesensors, units, and delivery ports may be located at various locationsalong the length of the rod. The IM rod 36 is secured to the bone withfasteners 45. The fasteners 45 may lock mechanically in the bone and/ormay thermally bond to the bone and rod. Examples of mechanical andthermal fasteners are disclosed in the thermoplastic implant documentsalready incorporated by reference.

With the rod 36 implanted, the microclimate may be controlled to createan optimal healing environment. For example, a sensor 14 may measure amicroenvironment parameter and based on predetermined levels, theelectronic processor 38 may instruct the reservoir controller 42 torelease a substance from the reservoir 40. Substances which may bebeneficial to a fractured bone may include bone morphogenetic proteins,antibiotics, hydroxyapitate, and other bone healing agents. Agents thatincrease or decrease the pH level may also be delivered. The electronicprocessor 38 may also instruct a heating/cooling unit 18 to change thetemperature of the body region. Controlling the microenvironment may beperformed automatically by microprocessors based on preset parameterlevels and input signals from the sensors. The microenvironment mayalternatively, or additionally, be controlled by a physician via remotecontrol. The physician may use RF, microwave, or IR energy to transmitinstructions to the microprocessors in the IM rod.

For use with the IM rod 36 of FIG. 3 or any other implant, amicroenvironment-controllable fastener 46 is provided in FIG. 4. Thefastener 46 may be made of metallic, ceramic, polymeric, composite, orthermoplastic material. The fastener 46 includes sensors 14,heating/cooling units 18, and electronic controllers 38 similar to thoseof FIG. 3. The sensors 14 may be temperature sensors, pH sensors,moisture sensors, oxygen sensors, carbon dioxide sensors, or othersensors to measure microenvironment characteristics. The heating/coolingunits 18 may be resistive heaters, ultrasonic heaters, IR heaters, RFheaters, microwave heaters, or convection/conduction cooling devices.Both the sensors 14 and heating/cooling units 18 are controlled by theelectronic controller 38, either automatically based on predeterminedmeasurements or manually via remote control. Manual control on theimplanted electronic processor may be achieved through IR, RF, ormicrowave energy or through an implanted wire.

The fastener 46 also includes delivery ports 16, a reservoir 40, and areservoir controller 42. Each delivery port 16 is in fluid communicationwith the reservoir 40 via piping 44. The delivery ports 16 and reservoir40 are configured for delivering a liquid, gas, gel, and/or solid toaffect the microenvironment of the region. The substance administeredthrough the delivery ports may be any of the substances disclosedherein. The reservoir controller 42 manipulates the release rate andrelease period of the substance(s) in the reservoir. The reservoircontroller 42 and electronic processor 38 may be linked together tofunction as a single system. That is, the reservoir controller andelectronic processor work together to control the microenvironment ofthe body region. Alternatively, the reservoir controller and electronicprocessor may be physically integrated into one assembly.

In use, the microenvironment of soft or hard tissue may be controlledwith the fastener 46 of FIG. 4. A bore may be created in the tissue, andthe fastener 46 positioned in the bore. Alternatively, the fastener 46may include a tissue-piercing tip 48 which eliminates the need to createa bore before implanting the fastener in the tissue. If the tissueincludes multiple areas for climate control, then the sensors 14, units18, and delivery ports 16 may be located at various locations along thelength of the fastener. With the fastener implanted, the microclimatemay be controlled to create an optimal healing environment.

In an exemplary embodiment, a sensor 14 may measure a microenvironmentparameter and based on predetermined levels, the electronic processor 38may instruct the reservoir controller 42 to release one or moresubstances from the reservoir 40. The electronic processor 38 may alsoinstruct a heating/cooling unit 18 to change the temperature of thetissue. Controlling the microenvironment around the fastener 46 may beperformed automatically by microprocessors based on preset parameterlevels and input signals from the sensors. The microenvironment mayalternatively, or additionally, be controlled by a physician via remotecontrol. The physician may use RF, microwave, or IR energy to transmitinstructions to the microprocessors in the fastener.

The fractured bone of FIG. 3 may alternatively, or additionally, bestabilized by a microenvironment-controlling rigid plate 50 of FIG. 5.The fastener 46 of FIG. 4 and IM rod 36 of FIG. 3 utilized internalmicroprocessors, sensors, and units. The implant 50 of FIG. 5 mayinclude externally mounted microenvironment-controlling devices. Therigid fixation plate may be made of metallic, ceramic, composite,polymeric, or thermoplastic material. The plate 50 includes sensors 14,heating/cooling units 18, and an electronic controller 38. The sensors14 may be temperature sensors, pH sensors, moisture sensors, oxygensensors, carbon dioxide sensors, or other sensors to measuremicroenvironment characteristics. The heating/cooling units 18 may beresistive heaters, an ultrasonic heaters, IR heaters, RF heaters,microwave heaters, or convection/conduction cooling devices. Both thesensors 14 and heating/cooling units 18 are controlled by the electroniccontroller 38, either automatically based on predetermined measurementsor manually with a wire or wireless (IR, RF, or microwave energy).

The rigid plate 50 also includes delivery ports 16, a reservoir 40, anda reservoir controller 42. Each delivery port 16 is in fluidcommunication with the reservoir 40 by way of piping 44. The deliveryports 16 and reservoir 40 are configured for delivering a liquid, gas,gel, and/or solid to affect the microenvironment of the region. Thesubstance administered through the delivery ports 16 may be any of thesubstances disclosed herein. The reservoir controller 42 manipulates therelease rate and release period of the substance(s) in the reservoir.The reservoir controller 42 and electronic processor 38 may be linkedtogether to function as a single system. That is, the reservoircontroller and electronic processor work together to control themicroenvironment of the body region. Alternatively, the reservoircontroller and electronic processor may be physically integrated intoone assembly.

The microenvironment of the bone fracture 34 may be controlled with therigid plate 50 alone, or with a combination of the IM rod 36, rigidplate 50, and/or fastener 46. In use, the rigid plate 50 may bepositioned against the bone 32 such that the sensors 14, heating/coolingunits 18, and delivery ports 16 are adjacent the fracture 34. If thebone 32 includes multiple fractures, then the sensors, units, anddelivery ports may be located at various locations along the length ofthe plate. The plate 50 may be secured to the bone with fasteners 45/46.The fasteners may lock mechanically in the bone and/or may thermallybond to the bone and rod. Examples of mechanical and thermal fastenersare disclosed in the thermoplastic implant documents alreadyincorporated by reference.

Where multiple implants are employed, it is contemplated that variouscomponents of the system, as described herein, may be distributed amongthe implanted elements. For example, each fastener may comprise areservoir and controllable port, and an intramedullary implant maycontain a controller, receiver, transmitter, and port controller,connected to the ports in the fasteners. A plate may further contain anenergy source in communication with the other implants, or may supportor contain any of the other components mentioned. Additionalcombinations and permutations for distributing components in accordancewith the invention are contemplated, while serving the objects of theinvention.

With the plate 50 implanted, the microclimate may be controlled tocreate an optimal healing environment. For example, a sensor 14 maymeasure a microenvironment parameter and based on predetermined levels,the electronic processor 38 may instruct the reservoir controller 42 torelease an agent or substance from the reservoir 40. Substances whichmay be beneficial to a fractured bone may include bone morphogeneticproteins, antibiotics, hydroxyapitate, and other bone healing agents.The electronic processor 38 may also instruct a heating/cooling unit 18to change the temperature of the body region. Controlling themicroenvironment may be performed automatically by microprocessors basedon preset parameter levels and input signals from the sensors. Themicroenvironment may alternatively, or additionally, be controlled by aphysician via remote control. The physician may use RF, microwave, or IRenergy to transmit instructions to the microprocessors on the plate.

In addition to controlling the microenvironment of a bone fracture, amicroenvironment-controlling implant may be utilized to heal tissuefollowing joint replacement surgery. FIG. 6 shows an intervertebral discreplacement component 60. The disc implant 60 may be advantageously madeof a biocompatible material, including metallic, ceramic, composite,polymeric, or thermoplastic material. Various intervertebral implantsand other implants which may include microenvironment-controllingdevices are disclosed in U.S. patent application Ser. No. 11/258,795filed Oct. 26, 2005, which is hereby incorporated by reference. Theintervertebral implant 60 of the present invention may include sensors14, heating/cooling units 18, and an electronic controller 38. Thesensors 14 may be temperature sensors, pH sensors, moisture sensors,oxygen sensors, carbon dioxide sensors, or other sensors to measuremicroenvironment characteristics. The heating/cooling units 18 may beresistive heaters, an ultrasonic heaters, IR heaters, RF heaters,microwave heaters, or convection/conduction or electronic coolingdevices. Both the sensors 14 and heating/cooling units 18 are controlledby the electronic controller 38, either automatically based onpredetermined measurements or manually via remote control. Manualcontrol on the implanted electronic processor may be achieved through IRor RF energy or through an implanted wire.

The intervertebral implant 60 also includes delivery ports 16, areservoir 40, and a reservoir controller 42. Each delivery port 16 is influid communication with the reservoir 40 via piping 44. The deliveryports 16 and reservoir 40 are configured for delivering a liquid, gas,gel, and/or solid to affect the microenvironment of the intervertebralregion. The substance administered through the delivery ports 16 may beany of the substances disclosed herein. The reservoir controller 42manipulates the release rate and release period of the substance(s) inthe reservoir. The reservoir controller 42 and electronic processor 38may be linked together to function as a single system. That is, thereservoir controller and electronic processor work together to controlthe microenvironment of the body region. Alternatively, the reservoircontroller and electronic processor may be physically integrated intoone assembly.

The microenvironment of adjacent vertebral bodies 62 may be controlledwith the implant 60 of FIG. 6 as follows. After the vertebral bodies 62have been prepared/cut, the implant 60 is positioned against thesuperior and inferior bones such that the sensors 14, heating/coolingunits 18, and delivery ports 16 are adjacent the bone. The implant 60may be secured to the bone with fasteners. The fasteners may lockmechanically in the bone and/or may thermally bond to the bone and rod.Examples of mechanical and thermal fasteners are disclosed in thethermoplastic implant documents already incorporated by reference.

With the disc component 60 implanted, the microclimate may be controlledto enhance tissue healing. For example, a sensor 14 may measure amicroenvironment parameter and based on predetermined levels, theelectronic processor 38 may instruct the reservoir controller 42 torelease a substance from the reservoir 40. Substances which may bebeneficial to a fractured bone may include bone morphogenetic proteins,antibiotics, hydroxyapitate, and other bone healing agents. Theelectronic processor 38 may also instruct a heating/cooling unit 18 tochange the temperature of the body region. Controlling themicroenvironment may be performed automatically by microprocessors basedon preset parameter levels and input signals from the sensors. Themicroenvironment may alternatively, or additionally, be controlled by aphysician via remote control. The physician may use RF, microwave, or IRenergy to transmit instructions to the microprocessors in the discimplant.

In addition to intervertebral implants, other joint replacementcomponents may include microenvironment-controlling devices. FIG. 7shows a total knee replacement implant 70 with climate adjusting meansof the present invention. The knee implant 70 may be made of metallic,ceramic, composite, polymeric, or thermoplastic material. Othermaterials and structural characteristics for knee replacement componentsare disclosed in U.S. Pat. No. 7,104,996 issued Sep. 12, 2006 and itscontinuations and divisionals, all of which are hereby incorporated byreference. The knee components 70 include sensors 14, heating/coolingunits 18, and an electronic controller 38. The sensors 14 may betemperature sensors, pH sensors, moisture sensors, oxygen sensors,carbon dioxide sensors, or other sensors to measure microenvironmentcharacteristics. The heating/cooling units 18 may be resistive heaters,an ultrasonic heaters, IR heaters, RF heaters, microwave heaters, orconvection/conduction cooling devices. Both the sensors 14 andheating/cooling units 18 are controlled by the electronic controller 38,either automatically based on predetermined measurements or manually viaremote control. Manual control on the implanted electronic processor maybe achieved through IR, RF, or microwave energy or through an implantedwire.

The knee replacement components 70 also include delivery ports 16, areservoir 40, and a reservoir controller 42. Each delivery port 16 is influid communication with the reservoir 40 by way of piping 44. Thedelivery ports 16 and reservoir 40 are configured for delivering aliquid, gas, gel, and/or solid to affect the microenvironment of theregion. The substance administered through the delivery ports 16 may beany of the agents or substances disclosed herein. The reservoircontroller 42 manipulates the release rate and release period of thesubstance(s) in the reservoir. The reservoir controller 42 andelectronic processor 38 may be linked together to function as a singlesystem. That is, the reservoir controller 42 and electronic processor 38work together to control the microenvironment of the body region.Alternatively, the reservoir controller and electronic processor may bephysically integrated into one assembly.

In use, the microenvironment parameters of adjacent bones of the kneemay be controlled with the knee replacement components 70 of FIG. 7.After the femur, tibia, and/or patella have been prepared/cut, thecomponents 70 are positioned against the joint bones such that thesensors 14, heating/cooling units 18, and delivery ports 16 are adjacenta cut surface of the bone. The components 70 may be secured to the boneswith fasteners. The fasteners may lock mechanically in the bone and/ormay thermally bond to the bone and rod. Examples of mechanical andthermal fasteners are disclosed in the thermoplastic implant documentsalready incorporated by reference.

With the knee components 70 implanted, the microclimate may becontrolled to create an enhanced healing environment. For example, asensor 14 may measure a microenvironment parameter and based onpredetermined levels, the electronic processor 38 may instruct thereservoir controller 42 to release a substance from the reservoir.Substances which may be beneficial to a fractured bone may include bonemorphogenetic proteins, antibiotics, hydroxyapitate, and other bonehealing agents. The electronic processor 38 may also instruct aheating/cooling unit 18 to change the temperature of the body region.Controlling the microenvironment may be performed automatically bymicroprocessors based on preset parameter levels and input signals fromthe sensors. The microenvironment may alternatively, or additionally, becontrolled by a physician via remote control. The physician may use RF,microwave, or IR energy to transmit instructions to the microprocessorsin the knee components.

Referring now to FIGS. 8A and 8B, a hip implant 80 may includemicroenvironment-controlling devices. An acetabular implant 80 isgenerally a half-spherical socket apparatus dimensioned to receive aball joint of the femur or femoral implant. The acetabular/ball jointimplant 80 may be made of metallic, ceramic, composite, polymeric, orthermoplastic material. Other materials and structural characteristicsfor acetabular component are disclosed in U.S. Provisional ApplicationNo. 60/810,080 filed Jun. 1, 2006, which is hereby incorporated byreference. The acetabular implant and/or ball joint implant 80 mayinclude sensors 14, heating/cooling units 18, and an electroniccontroller 38. The sensors 14 may be temperature sensors, pH sensors,moisture sensors, oxygen sensors, carbon dioxide sensors, or othersensors to measure microenvironment characteristics. The heating/coolingunits 18 may be resistive heaters, an ultrasonic heaters, IR heaters, RFheaters, microwave heaters, or convection/conduction cooling devices.Both the sensors 14 and heating/cooling units 18 are controlled by theelectronic controller 38, either automatically based on predeterminedmeasurements or manually via remote control. Manual control on theimplanted electronic processor may be achieved through IR or RF energyor through an implanted wire.

The hip implants 80 of the present invention may also include deliveryports 16, a reservoir(s) 40, and a reservoir controller 42. Eachdelivery port 16 is in fluid communication with the reservoir 40 viapiping 44. The delivery ports 16 and reservoir 40 are configured fordelivering a liquid, gas, gel, and/or solid to affect themicroenvironment of the hip region. The substance(s) administeredthrough the delivery ports may be any of the substances disclosedherein. The reservoir controller 42 manipulates the release rate andrelease period of the substance(s) in the reservoir. The reservoircontroller 42 and electronic processor 38 may be linked together tofunction as a single system. That is, the reservoir controller andelectronic processor work together to control the microenvironment ofthe body region. Alternatively, the reservoir controller and electronicprocessor may be physically integrated into one assembly.

In use, the microenvironment of adjacent hip bones 82 may be controlledwith the hip implant components 80 of FIGS. 8A and 8B. After the femurand/or hip bone 82 have been prepared/cut, the component(s) 80 arepositioned against the joint bones 82 such that the sensors 14,heating/cooling units 18, and delivery ports 16 are adjacent a cutsurface of the bone. The component(s) 80 may be secured to the boneswith fasteners. The fasteners may lock mechanically in the bone and/ormay thermally bond to the bone and rod.

With the acetabular/ball joint component(s) 80 implanted, themicroclimate may be controlled to create an optimal healing environment.For example, a sensor 14 may measure a microenvironment parameter andbased on predetermined levels, the electronic processor 38 may instructthe reservoir controller 42 to release a substance from the reservoir40. Substances which may be beneficial to a fractured bone may includebone morphogenetic proteins, antibiotics, hydroxyapitate, and other bonehealing agents. The electronic processor 38 may also instruct aheating/cooling unit 18 to change the temperature of the body region.Controlling the microenvironment may be performed automatically bymicroprocessors based on preset parameter levels and input signals fromthe sensors. The microenvironment may alternatively, or additionally, becontrolled by a physician via remote control. The physician may use RF,microwave, or IR energy to transmit instructions to the microprocessorsin the hip implants.

In FIGS. 9 and 10, a sheet-like implant 90 is configured for controllingthe microenvironment of tissue. The sheet 90 of FIG. 9 includesintegrated devices for controlling microenvironment parameters, whilethe sheet 92 of FIG. 10 includes externally mounted devices. The sheetsof FIGS. 9 and 10 may include a permeable mesh-like structure or mayinclude an impermeable structure. The sheets 90 and 92 may be made ofmetallic, ceramic, composite, polymeric, or thermoplastic material.Other materials, structural characteristics, and methods ofmanufacture/use for sheets are disclosed in U.S. Provisional Application60/810,080 filed Jun. 1, 2006, which was previously incorporated byreference. The sheets of FIGS. 9 and 10 may include sensors 14,heating/cooling units 18, and an electronic controller 38. The sensors14 may be temperature sensors, pH sensors, moisture sensors, oxygensensors, carbon dioxide sensors, or other sensors to measuremicroenvironment characteristics. The heating/cooling units 18 may beresistive heaters, an ultrasonic heaters, IR heaters, RF heaters,microwave heaters, or convection/conduction cooling devices. Both thesensors 14 and heating/cooling units 18 are controlled by the electroniccontroller 38, either automatically based on predetermined measurementsor manually via remote control. Manual control on the implantedelectronic processor may be achieved through IR or RF energy or throughan implanted wire.

The sheets 90 and 92 may also include delivery ports 16, a reservoir 40,and a reservoir controller 42. Each delivery port 16 is in fluidcommunication with the reservoir 40 by way of piping 44. The deliveryports 16 and reservoir 40 are configured for delivering a liquid, gas,gel, and/or solid to affect the microenvironment of the region. Thesubstance administered through the delivery ports 16 may be any of thesubstances disclosed herein. The reservoir controller 42 manipulates therelease rate and release period of the substance(s) in the reservoir 40.The reservoir controller 42 and electronic processor 38 may be linkedtogether to function as a single system. That is, the reservoircontroller and electronic processor work together to control themicroenvironment of the body region. Alternatively, the reservoircontroller and electronic processor may be physically integrated intoone assembly.

In use, the microenvironment of tissue may be controlled with the sheetsof FIGS. 9 and 10. As shown in FIG. 10, a sheet 92 is wrapped around abody conduit 94 such that the sensors 14, heating/cooling units 18, anddelivery ports 16 are adjacent the tissue of the conduit. The conduit 94may be a vessel, an intestine, an esophagus, or other tubular body part.The microenvironment-controlling sheet 90 and 92 of the presentinvention may be used to treat diseased blood vessels. In FIG. 10, ablood vessel 94 is illustrated with an aneurysm 96 therein. The sheet 92may be secured to the conduit with fasteners, and/or the sheet may befastened to itself to hold the sheet around the conduit 94. A sheet withthermoplastic material may be heated to shrink wrap the sheet to thebody conduit. Further disclosure on heat shrink implants may be found inU.S. Provisional Application No. 60/810,080 filed Jun. 1, 2006 which waspreviously incorporated by reference.

With the sheet 92 of the present invention implanted, the microclimatemay be controlled to enhance healing. For example, a sensor 14 maymeasure a microenvironment parameter and based on predetermined levels,the electronic processor 38 may instruct the reservoir controller 42 torelease a beneficial agent or substance from the reservoir 40. Theelectronic processor 38 may also instruct a heating/cooling unit 18 tochange the temperature of the body region. Controlling themicroenvironment may be performed automatically by microprocessors basedon preset parameter levels and input signals from the sensors. Themicroenvironment may alternatively, or additionally, be controlled by aphysician via remote control. The physician may use RF, microwave, or IRenergy to transmit instructions to the microprocessors in the sheets.

Magnetism/Charged Particles

In addition to the microenvironment-controlling devices described withrespect to FIG. 10, the implant 100 of FIG. 11 may include magnetsand/or electromagnets 102. The magnets 102 attract magnetically chargedparticles from adjacent tissue, such as particles in blood. It iscontemplated that any of the apparatus and methods disclosed herein mayinclude and use magnets and electromagnets. Other magnet/chargedparticle systems are disclosed in U.S. Pat. No. 6,820,614 entitled“Tracheal Intubination” and issued Nov. 23, 2004, which is herebyincorporated by reference.

Currently, there is no practical way to concentrate a pharmaceuticalagent to a local site. By charging pharmaceutical agents, cells, genetherapy agents, RNA, DNA, BMP, tissue inductive factors, etc., thesesubstances may be concentrated at a microenvironment region by a magnet.The charged substances would flow through the blood stream until anexternally mounted or internally implanted magnet draws the chargedparticle to a local region. The magnetic energy may also pull thechanged substances from the blood stream, through the vessel wall, andinto adjacent tissue.

Magnets may also be used to optimize blood flow by charging the iron ionin hemoglobin. The charged ion in hemoglobin could be concentrated at aspecific local microenvironment for improved oxygen flow. Nutrientdelivery, vasodilatation, vasoconstriction, cell membrane passage, cellreceptor activity may also be controlled by the magnetic charge and ironmolecules in the blood. Copper molecules/particles may also be chargedand concentrated at a local site with magnets.

The magnets used to attract charged particles may be placed in any ofthe microenvironment-controlling implants disclosed herein. In addition,the nano magnets or biodegradable magnets may be integrally formed intoa biodegradable polymeric or ceramic implant to form magnetic sinks. Themagnets may be disposed in polylactic acid or PEEK, for example, andimplanted in the body adjacent damaged tissue. The magnets may befragments of cobalt or samarium encapsulated by a polymer. Amagnetometer may be used to monitor and control the magnetic field ofthe sink. Increasing or decreasing the magnetic field, either internallywith a microprocessor and battery or externally with an external energysource, would control the blood flow of the vessel and/or concentratetherapeutic agents in the microenvironment region. The magnetic fieldmay be pulsed to compensate or represent heart pulses. Using a heartbeat sensor, the magnetic field pulses may be synchronized based on theheart rate.

Generally, the implant 100 of FIG. 11 may be cylindrical or tubular inshape to fit around a body conduit 94 such as a blood vessel. The innerdiameter D₁ of the cylindrical implant 100 may be less than the outerdiameter D₂ of the conduit 94 so that fluid flowing through the conduitit is inherently accelerated at the region of the implant. Theaccelerated flow of the fluid allows an increased amount of therapeuticagents to be delivery through the conduit wall and into the fluidstream. This characteristic is analogous to the Bernoulli's principle:flowing fluid accelerates at a region of decreased area/volume.

Cylindrical Implant

The implant 100 of FIG. 11 may be made of metallic, ceramic, composite,polymeric, or thermoplastic material. The cylindrical implant 100 mayinclude sensors 14, heating/cooling units 18, magnets 102, and anelectronic controller 38. The sensors 14 may be temperature sensors, pHsensors, moisture sensors, oxygen sensors, carbon dioxide sensors, orother sensors to measure microenvironment characteristics. Theheating/cooling units 18 may be resistive heaters, ultrasonic heaters,IR heaters, RF heaters, microwave heaters, or convection/conductioncooling devices. The magnets 102 may be earth magnets or electromagnets.The sensors 14, heating/cooling units 18, and magnets 102 are controlledby the electronic controller 38, either automatically based onpredetermined measurements or manually via remote control. Manualcontrol on the implanted electronic processor may be achieved through IRor RF energy or through an implanted wire.

The cylindrical implant 100 may also include port holes 16, areservoir(s) 40, a reservoir controller 42, and a suction means, such asan electric or manual pump. The port hole 16 may be in fluidcommunication with the reservoir 40 by way of piping 44. The port hole16 and reservoir 40 are configured for delivering a liquid, gas, gel,and/or solid to affect the microenvironment of the region. Thesubstance(s) administered through the delivery ports 16 may be any ofthe substances disclosed herein. The reservoir controller 42 manipulatesthe release rate and release period of the substance(s) in thereservoir. The reservoir controller 42 and electronic processor 38 maybe linked together to function as a single system. That is, thereservoir controller and electronic processor work together to controlthe microenvironment of the body region. Alternatively, the reservoircontroller and electronic processor may be physically integrated intoone assembly.

A port hole 16 may instead, or in addition to, be connected to thesuction means. The suction at the port hole would create a negativepressure (Venturi effect) on the surrounding tissue. The suction couldincrease blood flow by vasodilatation or draw blood away from a certaintissue area causing vasoconstriction. The negative pressure may also aidin the delivery and/or concentration of pharmaceutical substances. It iscontemplated that the other embodiments of the present invention mayalso include suction port holes, a suction pump, and associated tubing.For example, the knee replacement components 70 of FIG. 7 may includeport holes and a suction pump. This could improve vascular flow of kneetissue. The pump could be integrated into the implant such that as theknee is moved back and forth suction is created.

In use, the microenvironment of tissue may be controlled with thecylindrical implant 100. As shown in FIG. 11, the implant 100 ispositioned around a body conduit 94 such that the sensors 14,heating/cooling units 18, magnets 102, and delivery ports 16 areadjacent the tissue of the conduit. The conduit 94 may be a vessel, anintestine, an esophagus, or other tubular body part. For the sake ofdrawing simplicity, the inner diameter of the implant is generally thesame as the outer diameter of the conduit. However, as previouslydescribed, a smaller inner diameter of the implant would createincreased fluid flow thereby increasing the administration rate oftherapeutic agents. The microenvironment-controlling implant 100 of FIG.11 may be used to treat diseased blood vessels or other body lumens. Theimplant 100 may be secured to the conduit with fasteners and/or, theimplant may be fastened to itself to hold the implant around theconduit. A cylindrical implant with thermoplastic material may be heatedto shrink wrap the implant to the body conduit. Further disclosure onheat shrink implants may be found in patent document alreadyincorporated by reference.

With the cylindrical implant 100 of the present invention positioned,the microclimate may be controlled to create an optimal medical climate.For example, a sensor 14 may measure a microenvironment parameter andbased on predetermined levels, the electronic processor 38 may instructthe reservoir controller 42 to release a substance from the reservoir40. The electronic processor 38 may also instruct a heating/cooling unit18 to change the temperature of the body region and/or instruct themagnets 102 to energize thereby drawing charged particles to the conduitwall. The diameter of the cylindrical implant 100 may be increased ordecreased with the electronic processor 38 and the heating/cooling units18. Heating the implant may expand the implant diameter and cooling theimplant may decrease the diameter, or vice versa. Controlling themicroenvironment may be performed automatically by microprocessors basedon preset parameter levels and input signals from the sensors. Themicroenvironment may alternatively, or additionally, be controlled by aphysician via remote control. The physician may use RF, microwave, or IRenergy to transmit instructions to the microprocessors in the implant.

It is contemplated that other known surgical implants may include themicroenvironment-controlling devices described herein. For example, thepresent invention provides a microenvironment-controlling stent;cannula; catheter; spinal rod, plate, or pin; face and headreconstruction implant; shoulder replacement component; elbowreplacement implant; hand and foot implant, and other similar implants.

Climate Controlled Surgery

In addition to the apparatus previously described to control themicroenvironment of a living body, the present invention providesmethods and apparatus for performing climate-controlled surgery. Duringa surgical procedure, the body region being operated on is exposed tothe operating room environment. This is especially relevant duringmaximally invasive procedures but also relevant during minimallyinvasive surgery, endoscopic surgery, and insufflation. Usually, theoperating room is dry, and tissue response is affected by desiccation.The room temperature often varies between 60 and 65 degrees Fahrenheit,and the local tissue is cooled significantly. Also, when tissue is cutit releases enzymes which change the local pH. Bleeding changes thelocal pH as well. Irrigation is often used at the surgical region, butthe irrigation is not isotonic to decrease osmolarity and drug tension.Moreover, coolness and change in pressure effect vascular flow, causingvasoconstriction, therefore, fewer nutrients enter the wound site andless oxygen is delivered to the site which can further damage thetissue.

Using climate-controlled surgery, the local body temperature, not justthe core body temperature, may be regulated. Desiccation may beminimized, and vascular flow may be maintained. Also, oxygen tension andnutrient delivery may be optimized. The local pH level may becontrolled, and tissue osmolarity may be maintained.

Although a limited number of examples are provided herein, it iscontemplated that any type of surgery may be combined with theclimate-controlling methods herein. For example, the present inventionmay be applied to surgery of the foot and ankle, hand and wrist, elbow,knee, hip, shoulder, genitalia, head, etc. As will become clearersubsequently, surgery on a region of an extremity is most conducive forthe methods of climate-controlled surgery.

Referring now to FIG. 12, a system for climate-controlled knee surgeryis illustrated. The surgical system includes a hollow structure, such asan expanding cannula, or trocar 110, a microprocessor controller 112,sensors 14, heating/cooling units 18, magnets 102, reservoirs 40, pumps114 and related fluid conduit 116. The trocar 110 is dimensioned toenter the body region of the patient that is to be operated on. Thesensors 14 may be temperature sensors, pH sensors, moisture sensors,oxygen sensors, carbon dioxide sensors, or other sensors to measuremicroenvironment characteristics. The heating/cooling units 18 may beresistive heaters, an ultrasonic heaters, IR heaters, RF heaters,microwave heaters, or convection/conduction cooling devices. The magnets102 may be earth magnets or electromagnets. The sensors 14,heating/cooling units 18, magnets 102, reservoirs 40, and pumps 114 arecontrolled by the electronic controller 112, either automatically basedon predetermined measurements or manually via remote control. Manualcontrol on the implanted electronic processor may be achieved throughwire or wireless remote control. Wireless control may be performed withIR, RF, or microwave energy.

To perform climate-controlled knee surgery, a patient 118 may be placedin the prone position with the patient's leg to be operated onpositioned adjacent an edge of the support table 120. A leg cuff andstrap 122 may be connected with the patient's foot or ankle. The strap122 may be connected with an attachment point which may be movableup/down, left/right, or forward/backward.

Sensors 14 and/or magnets 102 may be attached to the patient's tissue inor around the incision area, positioned through trocar 110, or adjacentto the entry area. The sensors 14 and magnets 102 may be connected tothe controller via wires or wireless IR or RF energy. Fluid, such assaline, water, plasma, or other biocompatible fluid may be added to thetrocar 110 through the inlet pipe 116 via the pump 114. Alternatively,for insufflation, a gas may be added to trocar 110. The heating/coolingunit 18 may vary the temperature of the fluid during filling andthroughout the surgical procedure. Based on signals from the sensors 14and/or on the physician's direction, pharmaceutical or therapeuticagents stored in the reservoirs 40 may be selectively released into thefluid stream. The combination of agent reservoirs 40, heating/coolingunits 18, sensors 14, magnets 102, pumps 114, and fluid 126 forms ameans for creating, maintaining, and changing the environment of thesurgical region. During and after the operation, the fluid 126 may beextracted from the submersion tank 110 via the outlet pipe 116 b andvalve 128. The valve 128 may be controlled by the microprocessorcontroller and/or by the physician (shown).

One of reservoir 40 may advantageously contain a substance which may beused to control pH. It is advantageous to use a calcium based substancedue to a potentially beneficial effect on bones, although a wide varietyof substances may be used, as described above. The pH controllingsubstance may be a gas, liquid, or powder, and may enter the surgicalfield through a pipe 116 c and be collected through a separate pipe 116d. Adjustment of pH and temperature may advantageously be carried out toreduce postoperative pain.

Pump Implant

The present invention also provides an implantable pump for controllingthe microenvironment of a body region. The pump may control themicroenvironment parameters such as temperature, pH level, moisture,humidity, oxygen tension, carbon dioxide tension, rate of blood flow,nutrient-content, and the presence of pharmaceutical agents. Through theuse of pumps, reservoirs, sensors, and controllers, these parameters maybe measured, changed, and monitored, externally or internally.

In an exemplary embodiment, a pump system would control the localregulation of pH. pH-changing agents could be placed in an implantablepump which may be externally or internally controlled. Thepump/reservoir may include pH controlling agents such as calciumcarbonate or calcium sulfate. The pump could have valves which releasethe agents to the local circulation, or it could have an osmoticmembrane covering, another type of salt such as sodium chloride,potassium chloride, calcium carbonate, calcium sulfate. Calcium basedcompounds may be used because they are easily metabolized by the bodyand can help with issues of osteoporosis. Some salts, because of theirability to bind to proteins, may also be efficacious with pH control.The pH control system could also be ionic anionic. Certain salts thatare released may have an affinity to bind to proteins and affect thelocal microclimate.

Alternatively, a body region may be made more acidic. This can beaccomplished, for example, be delivering carbon dioxide (or a liquidcarbon dioxide) to tissue. As this agent is released it would createcarbonic acid which could make the pH more acidic. The pH level may beautomatically or manually controlled with sensors and a microprocessor.The sensors positioned locally in the tissue could detect the pH leveland could turn on and off the delivery of a pH-changing agent. The pHlevel could be varied during the course of the day, or during a timewhen one wants improved tissue effect.

Stomach Irritator

In a more specific embodiment, the pump system may be used as a stomachirritator. The pump system may be used for irritable bowel and bladderproblems as well. The stomach irritator could be used in place of or inaddition to gastric bypass surgery. The irritator could be a pHirritator or electromagnetic irritator. An electromagnetic irritator mayinclude electromagnets and a microprocessor for delivering magneticenergy to the stomach thereby decreasing the patient's appetite. The pHirritator system could create nausea by releasing viral agents orirritating agents to the stomach which would cause stomach muscle spasmand therefore decrease the patient's interest or desire to eat. Thesystem illustrated in FIG. 13 may include an electronic controller 38,sensors 14, magnets 102, heating/cooling units 18, delivery ports 16, areservoir 40, a battery 129, and related wire and conduit. Thesecomponents may be made of a biodegradable material. The batteries may berecharged with tissue flow, tissue movement, heat changes, thermalchanges, or pH changes. Other electrical generators and batteryrecharging devices and methods are described subsequently.

The irritator systems could be used as a temporary obesity treatment.The systems could be implanted transcutaneously, percutaneously,endoscopically, and/or minimally invasively. The implanted systems maybe fastened in place with thermoplastic bands, stapling, and/orultrasonic welding techniques described in patent documents incorporatedherein. The irritator systems of the present invention do not operate byreducing the volume of the stomach, rather the systems function likearrhythmia of the heart where an arrhythmia pattern in the stomach wallmusculature is created. This arrhythmia then inhibits normal mechanicaloperation of the stomach, and contributes to a feeling of bloatedness orfullness. The system may affect one or more locations of the stomach, itwould thus be diffuse affect, similar to creating gastric fibrillation.As previously described, the system may function electrically orelectromagnetically. It may also function ultrasonically where anultrasonic generator transmits vibratory energy to the stomach.Furthermore, the system may function thermally using heating unitsdescribed herein to create irritation-type spasm in the stomach.

In addition to the pH irritator and electromagnet irritator, the presentinvention provides a metallic ion irritator. This system may includemetallic ions to conduct temperatures of the stomach, bowel, bladder,etc. The metallic ions may be percutaneously implanted and activatedwith an electrical transmitter which may be external to the body,battery operated, and wearable by the patient. Thus, the patient orphysician may control the temperature of the stomach, etc. by changingthe signal of the transmitter.

Microenvironment Controlled Surgery of the Eye

Another embodiment of microenvironment-controlling surgery isillustrated in FIG. 14. The microenvironment-controlling devices of thepresent invention may be used to correct vision of the eye. The surgicalapparatus 130 includes a concave body 132, sensors 14, heating/coolingunits 18, delivery ports 16, reservoirs 40, and a microprocessorcontroller 38. The concave body 132 may be made of metallic, ceramic, orpolymeric material. In a specific embodiment, the concave body 132 is anultrasonic end effector capable of producing vibratory energy. Thesensors 14 may be temperature sensors, pH sensors, moisture sensors,oxygen sensors, carbon dioxide sensors, or other sensors to measuremicroenvironment characteristics. The heating/cooling units 18 may beresistive heaters, an ultrasonic heaters, IR heaters, RF heaters,microwave heaters, or convection/conduction cooling devices. The sensors14, heating/cooling units 18, and end effector (concave body) 132 may becontrolled by the electronic controller 38, either automatically basedon predetermined measurements or manually via remote control.

The apparatus of FIG. 14 also includes port holes 16, a reservoir(s) 40,a reservoir controller 42, and a suction means, such as an electric ormanual pump. The port hole 16 may be in fluid communication with thereservoir 40 by way of piping 44. The port hole 16 and reservoir 40 areconfigured for delivering a liquid, gas, gel, and/or solid to affect themicroenvironment of the region. The substance(s) administered throughthe delivery ports 16 may be any of the substances disclosed herein. Thereservoir controller manipulates the release rate and release period ofthe substance(s) in the reservoir 40. The reservoir controller 42 andelectronic processor 38 may be linked together to function as a singlesystem. That is, the reservoir controller and electronic processor worktogether to control the microenvironment of the body region.Alternatively, the reservoir controller and electronic processor may bephysically integrated into one assembly.

A port hole 16 may instead, or in addition to, be connected to thesuction means. The suction at the port hole 16 would create a negativepressure (Venturi effect) on the surrounding cornea tissue 134. Thenegative pressure may aid in the delivery and/or concentration ofpharmaceutical substances.

The microenvironment of the cornea 134 may be controlled during visioncorrection surgery with the apparatus 130 of FIG. 14 by the followingmethod. Initially, a physician will measure the uncorrected shape of thepatient's cornea 134 and determine the amount and location of reshapingnecessary to improve vision in the eye 136. With the calculationscompleted, the concave body 132 may be place in contact with the cornea134. Using the body 132 as an ultrasonic horn, vibration energy may beemitted to raise the temperature of the cornea 134 and reshape the outersurface. Before, during, and after reshaping, pharmaceutical agents maybe delivered to the cornea via the port openings 16, piping, andreservoir 40. The port openings 16 may also provide suction to thecornea 134 to draw the pharmaceutical agents to a specific location ordepth of the cornea. The sensors 14 may measure any of themicroenvironment parameters, such as temperature, acidity, etc. andprovide the measurements to the electronic controller. Theheating/cooling units 18 may be used to change the temperature of thecornea to optimize the reshaping and healing processes. Moreover,magnets 102 as described in early embodiments may be used to control themicroenvironment parameters of the cornea as well. All themicroenvironment-controlling devices (sensors, units, port openings,magnets, reservoir, etc.) may be automatically controlled by themicroprocessor, manually controlled by the physician, or a combinationof manual and automatic control.

Transdermal or Topical Delivery

Certain embodiments described thus far have beenmicroenvironment-controlling implants or surgical procedures. Theembodiments of FIGS. 15, 16, 17A, and 17B providemicroenvironment-controlling apparatus which are positioned againstskin. A topical pharmaceutical delivery system may administer drugslocally and transcutaneously and/or percutaneously. The system usespoloxamer lecithin organogel (PLO), lecithin isopropyl palmitate,polypropylene glycol, ethyl propylene glycol, ethoxydiglycol, and/orliposomal components to help dissolve or transport pharmaceutical agentsthrough the skin. While lecithin is a preferred substance, ketoprofen,licocaine, and steroids in concentrations of about 20 percent may alsobe resorbed through the skin.

Generally, as therapeutic agents are delivered topically, the diffusioncoefficient remains the same thereby releasing an agent at a constantrate. Physicians, however, may prefer that some pharmaceutical agents betopically administered at different rates depending on the need of thepatient or desire of the physician. The microenvironment-controllingdevices of the present invention may be used to selectively deliverytopical agents at various rates and periods. Raising the temperature orpH level, for example, may increase the diffusion coefficient, whilecooling the skin or lowering the pH level may slow drug delivery.Suction applied to the skin may also vary the drug flow rate. Thenegative pressure would create a Venturi effect in the skin which wouldenhance penetration through the skin and into an adjacent artery orvein. For example, a topical delivery system may be placed on the handto concentrate drug administration over the radial artery.

The types of pharmaceutical substances which may be delivered topicallyare well known in the art. These substances may be combined by themanufacturer in the factory or by the physician in thehospital/operating room to create a specific mixture, or cocktail ofdrugs that meet the patient's needs. These cocktails may be placed orincorporated into a gelatin, biologic foam, or biodegradable foam toabsorb through the skin and into the body. One type of gelatin which maybe used is pluronic gel. Pluronic gel or any other carrier may becombined with steroids, thrombolytic agents, pain relieving agents,opioids, lidocaine, anti-inflammatory agents, or chemotherapeutic agentsfor controlled topical local administration. Other pharmaceutical agentsdisclosed herein may be used with the topical system as well.

It is contemplated that the topical delivery system of the presentinvention may be combined with electroshock wave energy, RF energy, andelectromagnetic energy.

A topical pharmaceutical delivery patch 140 is illustrated in FIG. 15.The patch 140 may include a base sheet 142, sensors 14, heating/coolingunits 18, magnets 102, and microprocessor controllers 38. The base sheet142 may be similar to known patches such as the nicotine patch or birthcontrol patch. The sheet 142 may include an adhesive on the skin facingsurface. The sensors 14 may be temperature sensors, pH sensors, moisturesensors, oxygen sensors, carbon dioxide sensors, or other sensors tomeasure microenvironment characteristics. The heating/cooling units 18may be resistive heaters, an ultrasonic heaters, IR heaters, RF heaters,microwave heaters, or convection/conduction cooling devices. The magnets102 may be earth magnets or electromagnets. The sensors 14,heating/cooling units 18, and magnets 102 are controlled by theelectronic controller 38, either automatically based on predeterminedmeasurements or manually via remote control. Manual control of theelectronic processor may be achieved through IR or RF energy or throughan implanted wire.

The topical delivery system may also include port holes 16, areservoir(s) 40, a reservoir controller 42, and a suction means, such asan electric or manual pump. The port hole 16 may be in fluidcommunication with the reservoir by way of piping 44. The port hole 16and reservoir 40 are configured for delivering a liquid, gas, gel,and/or solid to affect the microenvironment of the region. Thesubstance(s) administered through the delivery ports 16 may be any ofthe substances disclosed herein. The reservoir controller 42 manipulatesthe release rate and release period of the substance(s) in thereservoir. The reservoir controller 42 and electronic processor 38 maybe linked together to function as a single system. That is, thereservoir controller and electronic processor work together to controlthe microenvironment of the body region. Alternatively, the reservoircontroller and electronic processor may be physically integrated intoone assembly.

A port hole 16 may instead, or in addition to, be connected to thesuction means. The suction at the port hole 16 would create a negativepressure on the surrounding tissue. The suction could increase bloodflow by vasodilatation or draw blood away from a certain tissue areacause vasoconstriction. The negative pressure may also aid in thedelivery and/or concentration of pharmaceutical/therapeutic substances.

In an exemplary method of use, the patch of FIG. 15 may control themicroenvironment of soft tissue, such as skin. The patch 140 ispositioned against the skin such that the sensors 14, heating/coolingunits 18, magnets 102, and delivery ports 16 are adjacent the tissue.The patch 140 may be secured to the skin with adhesive. With the patchpositioned, the microclimate may be controlled to create an optimaltopical drug delivery. For example, a sensor 14 may measure amicroenvironment parameter and based on predetermined levels, theelectronic processor 38 may instruct the reservoir controller 42 torelease a substance from the reservoir 40. The electronic processor 38may also instruct a heating/cooling unit 18 to change the temperature ofthe body region, instruct the magnets 102 to energize thereby drawingcharged particles to the skin, and/or instruct increased or decreasedflow rate of the therapeutic agent. Controlling the microenvironment maybe performed automatically by microprocessors based on preset parameterlevels and input signals from the sensors. The microenvironment mayalternatively, or additionally, be controlled by a physician via remotecontrol. The physician may use RF, microwave, or IR energy to transmitinstructions to the microprocessors in the implant.

Ultrasonic Topical Drug Delivery

Referring now to FIG. 16, an ultrasonic topical drug delivery system 144may control the microenvironment of soft tissue. The ultrasonic system144 may include a main body 146, sensors 14, heating/cooling units 18,delivery ports 16, reservoirs 40, and a microprocessor controller 38. Ina specific embodiment, the body 146 is an ultrasonic end effectorcapable of producing vibratory energy. The sensors 14 may be temperaturesensors, pH sensors, moisture sensors, oxygen sensors, carbon dioxidesensors, or other sensors to measure microenvironment characteristics.The heating/cooling units 18 may be resistive heaters, an ultrasonicheaters, IR heaters, RF heaters, microwave heaters, orconvection/conduction cooling devices. The sensors 14, heating/coolingunits 18, and end effector (concave body) 146 may be controlled by theelectronic controller 38, either automatically based on predeterminedmeasurements or manually via remote control.

The ultrasonic topical system 144 also includes port holes 16, areservoir(s) 40, a reservoir controller 42, and a suction means, such asan electric or manual pump. The port hole 16 may be in fluidcommunication with the reservoir 40 by way of piping. The port hole 16and reservoir 40 are configured for delivering a liquid, gas, gel,and/or solid to affect the microenvironment of the region. Thesubstance(s) administered through the delivery ports may be any of thesubstances disclosed herein. The reservoir controller 42 manipulates therelease rate and release period of the substance(s) in the reservoir.The reservoir controller 42 and electronic processor 38 may be linkedtogether to function as a single system. That is, the reservoircontroller and electronic processor work together to control themicroenvironment of the body region. Alternatively, the reservoircontroller and electronic processor may be physically integrated intoone assembly.

A port hole 16 may instead, or in addition to, be connected to thesuction means. The suction at the port hole 16 would create a negativepressure (Venturi effect) on the surrounding tissue 148. The negativepressure may aid in the delivery and/or concentration of pharmaceuticalsubstances.

The microenvironment of skin may be controlled during topicaladministration of a pharmaceutical substance. In use, the ultrasonicdrug delivery system 144 of FIG. 16 may be positioned against softtissue, such as skin 148. To administer a pharmaceutical agent 150 tothe skin 148, the operator/physician may utilize any of themicroenvironment-controlling devices. For example, the end effector 146may transmit vibratory energy to the skin 148, and the heat/coolingunits 18 may change the temperature of the skin. A substance 150 may bedelivered from the reservoir via the port openings 16. The substance 150may be any of the agents disclosed herein, such as a pH-changing agent.The port openings 16 may alternatively, or additionally, providenegative pressure to the skin. The magnets 102 of the system may attractchanged particles to the skin for drug concentration. All of thesemicroenvironment-controlling devices permit the microenvironmentparameters to be measured, changed, and monitored. A microprocessor mayautomatically control the devices, or a physician may control thedevices and parameters manually.

Blood Loss

It is contemplated that the apparatus and methods of FIGS. 15 and 16 mayfurther be used to stop bleeding. The systems may deliver individualdrugs or drug cocktails to the bleeding tissue while changing andmonitoring the microenvironment parameters. Examples of substances thesystems may used to control bleeding include epinephrine, sucroseproducts as a vasoconstrictor, tetracycline to increase or decreasescarring, and soluble gels.

Iontophoresis

Controlling the microenvironment of tissue may also be combined withiontophoresis, a form of electro-osmosis. Currently, physical therapistsare using iontophoresis to help penetrate cortisone into the skin. Anelectric charge is placed between electrodes positioned adjacent theskin. The electric current aids in topical drug administration. Thistechnique may be combined with devices and methods for controlling themicroenvironment parameters of a region of the body. Along with theelectric current, the temperature (ultrasound), pH level, moisture,humidity, porosity, pressure, and other parameters may be changed andmonitored. Instead of having a constant current, the electric charge maybe oscillated, pulsed, or alternated during topical drug delivery, andinstead of using iontophoresis for applying therapeutic agents to theskin, the technique may be used for intracorporeal drug delivery toother tissue, such as bone, muscle, and cartilage, as well.

Any of the pharmaceutical agents disclosed herein may be combined withiontophoresis techniques. In addition, certain cellular elements such asDNA, RNA, BMPs, protein, hormones, fetal cells, or other cellularelements may be included in a tissue scaffold or tissue graft which maybe implanted and iontophoretically delivered. The cellular elements maybe driven into tissue, like bone matrix, with or without an implantablescaffold or graft. The system could be a closed system left inside thebody where electrical energy is used to drive cells, such as mesenchymalor stem cells, or other therapeutic agents into tissue. Alternatively,the system may be positioned partially outside the body with only theelectrodes and microenvironment-controlling devices implanted.

FIGS. 17A and 17B illustrate an exemplary embodiment of an iontophoreticsystem. In FIG. 17A, a device 160 for iontrophoretic treatment is shownpositioned on the surface of a patient's skin 162. As previouslydescribed, the iontrophoretic device 160 of the present invention may befully or partially implanted for delivery of therapeutic agentsintracorporeally. The device 160, as illustrated in FIG. 17B, includes acylindrical body 164 made of a biocompatible material, such as metal orplastic. Electrical components such as a microprocessor and power supplyare located in an upper compartment 166, while reservoirs are positionedin a lower compartment 168 of the body 164. Between the upper and lowercompartments is a pair of iontophoretic electrodes 170, typically ofelectrically conductive silicone/carbon material, and which areseparated from each other by a divider baffle. The electrodes 170 areconnected to the electrical components. A power recharge port orreservoir refill port 172 may be located on the cylindrical body 164.Operation of the iontophoretic device 160 may be via a control station174 which includes a screen and selector buttons. For an implantableiontophoretic device, operation may be through RF, microwave, or IRenergy.

The iontophoretic device of FIGS. 17A and 17B may include means forcontrolling all the microenvironment parameters. Also, it iscontemplated that the implants and methods previously disclosed forcontrolling the microenvironment of the body region may also include aniontophoretic drug delivery system.

Dementia

Microenvironment control may further be used to prevent or treatdementias. Currently, it is believed that Alzheimer's disease may berelated to decreased temperature and decreased blood flow to the brain.Existing pharmaceuticals such as Aricept may increase blood flowslightly. Other studies suggest possible cognitive function, walkingexercises, or reading exercises may improve overall cognitive function.The present invention provides control of the microclimate of the brain,specifically vascular flow, temperature, and other factors such as pH,electrical stimulation, electromagnetic, etc. This relates to diurnalcurve. The temperature or blood flow would not be constant, but would becontrolled regularly. This could be related to the cortisone levels inthe body or could be a diurnal control where it might be warmest atcertain parts of the day and cooler, but could potentially track thepatient's normal temperature curves, being lowest at 8:00 AM and highestat 8:00 PM. It could also match serum cortisol levels. Themicroenvironment parameters may be changed or given multiple spikesduring the course of the day. Normally, there is not a constant increasein temperature; rather, it could fluctuate or vary. Controlling thetemperature could also be combined with physical exercises or cognitivefunction exercises.

One objective of microenvironment control is to increase thetemperature/blood flow to the brain. This could be done by mechanical,electrical, or thermal devices for the head, neck, or for the carotidvasculature, for example. This may be performed with 1) electricalcontrol—a heating/cooling unit could be ultrasound, RF, electromagnetic,fluid controlled, convention or conduction cooling, etc.; 2) mechanicalcontrol—a hat or a turtleneck neck warmer could be used to warm theblood flow to the brain, and it could be made of a material which allowspharmaceuticals to be delivered transcutaneously (Venturi effect); 3)technique control—the location and timing of heating/cooling units couldaffect the temperature curves; 4) cognitive features—an active brainundergoing an activity, learning, study tools, activity tools, whichwould also essentially increase temperature, blood flow, but incombination with the blood flow curves; and 5) pharmaceutical treatmentswhich would improve vascular flow, vasodilatation—vasodilators such asnitroglycerin or transcutaneous medication may be transcutaneouslydelivered over the carotid arteries through a Venturi type effect.

The reverse could also occur in children that may be, for example,hyperactive or patients that are having seizures. These conditions maybe controlled by performing exactly the opposite: cooling and decreasingthe blood flow selectively, or decreasing the overall core temperatureof the brain or selective locations with the brain. This could be doneexternally, internally, transcutaneously, percutaneously, etc.

In addition to dementias and hyperactivity, it is contemplated thatother diseases or disorders such as sleep apnea, hypothermia, andarthritis may be prevented or treated by controlling themicroenvironment parameters.

Body Suit/Worn Items

FIGS. 18-21 illustrate various, non-limiting, embodiments ofmicroenvironment-controlling outerwear. A cap 180 is shown in FIG. 18,while a neck scarf 190 is illustrated in FIG. 19. The cap 180 covers thepatient's head from the orbital ridge to the base of the skull mediallyand from the ventral aspect of the head down laterally to the base ofthe skull below the ears. The scarf 190 wraps around the patient's neck.By altering the head/neck temperature with the cap/scarf,vasoconstriction or vasodilatation would decrease or increase bloodflow. The cap 180/scarf 190 includes a microprocessor 38 and a pluralityof sensors 14, magnets 102, and heating/cooling units 18. The sensors 14may be temperature sensors, pH sensors, moisture sensors, oxygensensors, carbon dioxide sensors, or other sensors to measuremicroenvironment characteristics. The heating/cooling units 18 may beresistive heaters, an ultrasonic heaters, IR heaters, RF heaters,microwave heaters, or convection/conduction cooling devices. The magnets102 may be earth magnets or electromagnets. The magnets 102 may be usedto alter blood flow and increase circulation. The cap 180 may alsoinclude ear cannel inserts to monitor core temperature and balance thetemperature with a heating/cooling unit in the cap. The sensors 14,heating/cooling units 18, inserts, and magnets 102 are controlled by themicroprocessor controller, either automatically based on predeterminedmeasurements or manually via remote control.

A microenvironment-controlling body suit 200 is shown in FIG. 20, and aglove 210 is illustrated in FIG. 21. The suit 200 covers the patient'storso, arms, and legs. The glove 210 is configured to cover thepatient's hand and wrist. By altering the temperature with thesuit/glove, vasoconstriction or vasodilatation would decrease orincrease blood flow. The suit 200/glove 210 includes a microprocessor 38and a plurality of sensors 14, magnets 102, and heating/cooling units18. The sensors 14 may be temperature sensors, pH sensors, moisturesensors, oxygen sensors, carbon dioxide sensors, or other sensors tomeasure microenvironment characteristics. The heating/cooling units 18may be resistive heaters, an ultrasonic heaters, IR heaters, RF heaters,microwave heaters, or convection/conduction cooling devices. The magnets102 may be earth magnets or electromagnets. The magnets 102 may be usedto alter blood flow and increase circulation. The sensors 14,heating/cooling units 18, inserts, and magnets 102 are controlled by themicroprocessor controller 38, either automatically based onpredetermined measurements or manually via remote control.

Therapeutic Bacteria

In a related aspect of the invention, bacteria may be used to controlthe microenvironment. The previously described reservoirs associatedwith microenvironment-controlling devices may further include bacteriafor changing microenvironment parameters. Alternatively, oradditionally, bacteria may be placed in a mesh-like sac, with or withoutother therapeutic agents. In an exemplary embodiment, bacteria which areeasily tolerated or symbiotic with the body, such as normal flora, maybe seeded in tissue to control, for example, the pH level. Some toxicbacteria which require controlling in the body include staph aureus ormethicillin resistant staph aureus (MRSA). If a patient has an infectionwith MRSA, a physician may want to affect the pH level by varying thelevel during the course of the day. Implanted bacteria may also controllocal blood flow, oxygen tension, and other microenvironment parameters.

In another exemplary embodiment, certain types of e-coli may be verywell tolerated by the body, and not toxic, or have been made lessviable. There are also various bacteroides and bactericides which arewell tolerated. These could be used to displace staph aureus in theright pH environment. Therefore, physicians could use therapeuticbacteria to fight off dangerous bacteria. The therapeutic bacteria beingnormally tolerated by the body could then be killed off, removed, or ifthe microclimate changes the therapeutic bacteria could be eradicated.It is contemplated that physicians could do the same with other types ofsymbiotic organisms, different types of parasites or saprophytes, aswell as different types of viral approaches to fighting off an infectionby seeding the tissue with another infection and controlling themicroenvironment parameters, such as pH level, oxygen tension,temperature, etc. Once the acute infection or the more severe infectionis resolved then the physician can more easily manage the localinfection.

To help further describe the use of bacteria to fight diseases, ananalogy is provided with respect to the processing of sausage. Duringmanufacture, sausage is dry cured giving it a different smell anddifferent flavor. During this process, bacteria which produces lacticacid act as a fermenting agent. The bacteria add to the flavor, but theyalso have preservative properties. The acid and other compounds kill offother bacteria that spoil food. This same principle may be applied tokilling off unwanted bacteria causing caustic infections in the body, aspreviously described. The use of bacteria or other targeting substancemay be combined with control of the microenvironment parameters. Thebacteria in sausage are lactobacillus casei. These bacteria are able tofunction in very low oxygen tensions, high salt concentrations, and lowoxygen conditions. A physician could induce these conditions locally tofight off local infections then change the oxygen tension to ultimatelykill off the lactobacillus. Lactobacillus is a facultative anaerobe andcould be delivered transcutaneous, percutaneously, etc. to the infectionsite of the patient.

Wicking Agent

The therapeutic bacteria, or any pharmaceutical agent, may also place ina reservoir located in a biodegradable screw or hollow biodegradableobject. The implant could have a wicking action which could wick thebacteria/agent over to another material such as a scaffold or collagen.Wicking action includes capillary action, capillarity, or capillarymotion. For example, periapatite or hydroxyapatite could be wickedthrough or around the exterior surface of an implant, allowing for anincreased distribution area. The wicking agent may be a porous ceramic,polymer, composite, or fabric. It may be biodegradable and flexible. Inan exemplary embodiment, a biodegradable porous site may be attached toa periapatite acetabular shell so BMP, antibiotics, or other agents maybe delivered over the entire surface of the shell by simply allowing itto wick from a hollow biodegradable implant or reservoir.

It is contemplated that the wicking means for delivering a therapeuticagent may be combined with the other microenvironment-controllingdevices described herein. That is, in addition to sensors, magnets,reservoirs, and heating/cooling units, a wicking agent may be used todeliver therapeutic agent to control the microenvironment. The wickingaction may be controlled automatically by the microprocessor controllerof the implant and/or manually by a physician via remote control or RF,IR, microwave energy. Wicking control includes methods describedelsewhere herein, and including ports, closable portals, retractable ormovable wicking material, and movable seals.

Implantable Filter

In another related aspect, the present invention provides implantablefilters and methods of their use. The implantable filter may bepositioned in the body to capture cellular material, proteins, enzymes,or other body substances. A fistula may be created between two bodyparts such as two organs, and a filter may be positioned in the fistulato gather body substances. For example, a blood filter may be placed inthe vasculature or a side channel of a blood vessel which selectivelytraps white cells and immunoglobulins. The filter may be implanted for ashort period of time, i.e. minutes (during an operation), or could beleft in place for a longer period of time (between surgical procedures).The filter could be a porous collagen filter, a porous polylactic acid,a PGA compound, or other known filter material. When sufficientsubstance has been captured, the filter may be removed, for examplepercutaneously, and re-implanted in infected tissue or where healthytissue cells are needed.

An implantable filter may also be placed in a joint or synovial site toharvest cartilage cells. The filter may be connected with a tissuescaffold. The scaffold could be left floating in the joint, and whilethe joint moves, cells or slough from the joint surface may be capturedin the filter. These captured cells could then be implanted into a jointdefect or in a different joint to repair surface defects. The scaffoldand cells may be used in combination with pressed or shaped bone orbone-like products, such as OP-1. In an exemplary use, thescaffold/cells may be osteoinductive and/or cartilage inductive toresurface a joint. In addition, the scaffold/cells may be sculpted ormolded in situ or in the operating room and fastened in place withdifferent types of thermal bonding agents, adhesives, polysaccharides,etc.

In another embodiment, the joint filter (and scaffold) may be affixed tothe joint tissue. Movement of the knee joint would allow cells topopulate this membrane to allow healing of cartilage lesions/biologicresurfacing. Implantation of the joint filter may be performed withcomputer navigation and imaging technology. The joint tissue may becontoured to form fit the scaffold/filter. To fasten the filter totissue, it may be tissue welded with biocompatible temperatures andmolded to the surface of the bone such as with ultrasonic welding. Forexample, the filter may conform to the articular surface so that itwould have a smooth contour with the biologic or biodegradable filter ormembrane attached.

To induce cells into the filter, body movement may be used to create ahydraulic effect or Venturi effect. Alternatively, or additionally, themembrane or filter could have a suction type pump that could be builtinto it which would create negative pressure, either constantly or atvariable times during the course of the day. This could be internally orexternally controlled. The suction would deliver or pull cells into thecenter of the filter/membrane/matrix to populate cells in a threedimensional portion of the matrix. The suction could be delivered with apump, electrically or electromagnetically. To determine when the filterhas been sufficiently populated, a physician could use ultrasoundenergy, density determination, MRI, CT scan, or other similar volumetricmeasuring methods.

An implantable filter may also be placed in bone marrow. As the bonemarrow moves, either naturally or through external pressure/suction,stem cells could be selectively harvested through the filter. The filterand cells may be removed from the bone marrow during the same procedureor during another surgical procedure. The filter and/or stem cells maythen be implanted at the local tissue site (i.e. heart, brain, spinalcord, or other organ). In an exemplary embodiment, the filter ispercutaneously implanted in bone marrow of the hip. It could beimplanted and removed during the same procedure or could be left in fora period of hours or days and then could be removed. The harvested cellsand/or filter could be compressed or shaped and placed into a defect,such as a damaged heart muscle.

Cells captured with a filter of the present invention may also be usedin peripheral muscle, cartilage graft, bone graft, or other implant. Thecells and/or filter could further be used on the surface of jointreplacement components.

In a further exemplary embodiment, a filter may be implanted in apatient's eye to collect retinal cells. The captured cells may beharvested from the filter and used to prevent or treat maculardegeneration or another eye tissue injury. The harvested retinal cellsalong with the filter may be implant in the eye. In this configuration,the filter/cells may be used to treat macular degeneration, where thedegeneration may be caused by a chlamydial infection. To do so,antibiotics, tetracycline, doxycycline, and other therapeutic agents maybe placed on or impregnated in the filter. The agent(s) may be timereleased locally to help cool off the chlamydial infection within theeyeball/retina itself. This embodiment is particularly beneficialbecause antibiotics and other substances do not go through the bloodbrain barrier and do not get into the tissue inside the eyeball.

Various methods of use are contemplated for the cell filters of thepresent invention. For example, a fistula may be formed between anartery and vein, and the filter could be placed in the fistula topermanently harvest cells. The filter then could have tubing which coulddeliver the captured cells to another site in the body. An implantedfilter could be left within bone marrow to trap cells. Then, through aclosed line which could be subcutaneously implanted to another tissuelocation, the cells could be transported to a transplant site whilemaintaining the cells viable by body fluid. The simple movement of bodyparts, organs, blood movement, etc., would trap these cells in thefilter and move the cells to the recipient site.

The filters of the present invention may include different porosity totrap different types of cells. They could have adhesives such aspolysaccharide adhesives, or certain ionic or covalent attractions forcertain types of cells. The filters may also be coated it withimmunoglobulins or other pharmaceuticals or proteins to attract or bondcertain types of white cells, red cells, or blood marrow elements.

In a further filter embodiment, an implantable filter may be positionedin the amniotic membrane, either free floating or attached to onesurface of the membrane. As the fetus is moving, cells are sloughed offand will be caught by the filter/mesh. The filter/mesh could then besent off to cell culture, be stored in a tissue bank, or be reimplantedin the same patient or another patient. The captured cells may include,for example, dedifferentiated stem cells, mesenchymal cells, embryonalcells, and fetal cells. The fetus would be untouched and would maintainits viability. The filter may be implanted and removed through anexpandable cannula, under fluoroscopic visualization, or ultrasonicguidance without damaging the fetus.

Similarly, a filter of the present invention could be used to attach orgrasp tissue cells on the surface of the heart. If a person has a heartattack, the victim could lose muscle cells in one portion of the heart,while another portion of the heart may remain viable. An implantablefilter may be positioned in that portion of the heart that remainsviable. As the heart moves, certain cardiac cells would be trapped intothe filter. The filter and/or cells could then be removed at the samesurgical time or during another surgical procedure. The cells may betransplanted into the area where the cardiac cells are dead to inducecardiac cell formation. These cells could be combined with bone marrowcells, OP-1, and other tissue inductive factors to enhance growth.

All of the above described filters may be placed within or on thesurface of any type of tissue. The porosity, surface area, and/orcontour of filter may be used to entrap or capture cells. To aid in cellcollection, negative pressure, such as a sponge which would apply slownegative pressure, could be applied to the filter and surrounding area.A sponge would draw collected cells to the center of the matrix,progressively populating the entire matrix.

FIGS. 22 and 23 illustrate exemplary embodiments of the filters of thepresent invention. In FIG. 22 the filter 220 is generally shaped like acircular parachute or sea anchor, while the filter 230 of FIG. 23 isgenerally flat. The filters may include metallic, ceramic, composite,polymeric, or thermoplastic material. The filters may include amesh-like structure and may be flexible or rigid and biodegradable orbiostable. The filters may include sensors 14, heating/cooling units 18,magnets 102, and an electronic controller 38. The sensors 14 may betemperature sensors, pH sensors, moisture sensors, oxygen sensors,carbon dioxide sensors, or other sensors to measure microenvironmentcharacteristics. The heating/cooling units 18 may be resistive heaters,an ultrasonic heaters, IR heaters, RF heaters, microwave heaters, orconvection/conduction cooling devices. The magnets 102 may be earthmagnets or electromagnets. The sensors 14, heating/cooling units 18, andmagnets 102 are controlled by the electronic controller 38, eitherautomatically based on predetermined measurements or manually via remotecontrol. Manual control on the implanted electronic processor may beachieved through IR, RF, or microwave energy or through an implantedwire.

The filters 220/230 may also include port holes 16, a reservoir(s) 40, areservoir controller 42, and a suction means, such as an electric ormanual pump. The port hole 16 may be in fluid communication with thereservoir 40 by way of piping. The port hole 16 and reservoir 40 areconfigured for delivering a liquid, gas, gel, and/or solid to affect themicroenvironment of the region. The substance(s) administered throughthe delivery ports may be any of the substances disclosed herein,including bacteria. The reservoir controller 42 manipulates the releaserate and release period of the substance(s) in the reservoir. Thereservoir controller 42 and electronic processor 40 may be linkedtogether to function as a single system. That is, the reservoircontroller and electronic processor work together to control themicroenvironment of the body region. Alternatively, the reservoircontroller and electronic processor may be physically integrated intoone assembly.

A port hole 16 may instead, or in addition to, be connected to thesuction means. The suction at the port hole 16 would create a negativepressure (Venturi effect) on the surrounding tissue. The suction wouldincrease the capture rate of cells. The negative pressure may also aidin the delivery and/or concentration of pharmaceutical substances.

Methods of using the filters 220/230 of the present invention have beenpreviously illustrated. That is, the filters may be implanted in thevasculature, bone marrow, fistula, organ, etc. to collect desired cellsand other body substances. The filter 230 of FIG. 23 is particularlyapplicable to muscle, joint, organ, or bone repair as previouslydescribed. The filter 230 may be contoured or shape to form to thesurface of tissue. With the filters implanted, the microclimate may becontrolled to create an optimal cell/substance capturing climate. Forexample, a sensor 14 may measure a microenvironment parameter and basedon predetermined levels, the electronic processor 38 may instruct thereservoir controller to release a substance from the reservoir. Theelectronic processor 38 may also instruct a heating/cooling unit 18 tochange the temperature of the body region and/or instruct the magnets102 to energize thereby drawing charged particles to the conduit wall.Controlling the microenvironment may be performed automatically bymicroprocessors based on preset parameter levels and input signals fromthe sensors. The microenvironment may alternatively, or additionally, becontrolled by a physician via remote control. The physician may use RF,microwave, or IR energy to transmit instructions to the microprocessorsin the implant.

Aerosol Delivery

In another related invention, therapeutic and pharmaceutical agents maybe delivered to body tissue in a pulsed, atomized manner. The followingdescription of a pharmaceutical agent distribution system may be used incombination with and/or integrated with the microenvironment-controllingapparatus and methods described herein. Generally, during the course ofmedical treatment, medicaments are administered to patients before,during, and after surgery. In many medical situations it is necessary ordesirable to administer small amounts of medicaments and otherpharmaceutical agents to a patient over a relatively long period oftime.

For example, heparin is administered to a patient in need thereof by anintravenous “drip” procedure. Other medicines which may be administeredthrough the “drip” process include antiarrhythmics, vitamins, hormones,corticosteroids, anesthetics and antibiotics. These medicines may beadministered intermittently by bolus injection or continuously bygravity dispensers. Bolus injections may not, however, match thepatient's actual requirements and may subject the patient to largerdosages of drugs than required as well as frequent needle insertion.Drug delivery through gravity dispensers may limit the patient'slifestyle by tethering the patient to the intravenous drip apparatus.Furthermore, the dispensing rate is not always constant.

Rather than relying on the manual injection of bolus doses of drugsusing syringes or on manually setting the drip rate of gravity-fedintravenous infusion sets, health professionals are utilizing infusiondevices that electronically or mechanically control the infusion rate ofdrugs as they are being administered to patients. Infusion pumps mayinclude compact pump housings or larger stationary pump housing units.The administration of prescribed drugs has been accomplished throughinfusion tubing and an associated catheter or the like, therebyintroducing the drug intravenously. Pain, tissue damage and post-opcomplications have long been tolerated as negative side effects from theuse of existing hypodermic drug delivery infusion systems. The pain andtissue damage are a direct result of uncontrolled flow rate inconjunction with excessive pressures created during the administrationof drug solutions within the tissue spaces. Also, it has beendemonstrated that particular pressures for a specific tissue type willcause damage. It is therefore critical that a specific flow rate inconjunction with a specified pressure range be maintained during thedelivery of fluids (drugs) when a subcutaneous injection is givenpreventing pain response as well as tissue damage.

The most common application of infusion devices is for the maintenanceof appropriate fluid levels in patients. Fluid therapy is commonly usedin the treatment of burns, the pre- and postoperative management ofsurgical patients and in the treatment of dehydration. Theadministration of drugs provides the greatest challenge to infusiondevices. For a drug to be effective, the concentration of any drug atits site of action must be sufficiently high for the drug to beeffective, yet the concentration must not be too high for the drug tobecome toxic to the patient.

Used in applications such as delivering anesthetics during surgery,chemotherapy for cancer, and oxytocic agents for inducing labor,continuous drug infusion reduces the fluctuations in a drug'sconcentration that occurs with the more traditional modes of drugadministration such as injections and pills. Moreover, continuous druginfusion assures a continuous therapeutic action as long as the infusionrate is appropriate.

In contrast to continuous drug infusion pumps, some infusion pumpsdeliver drugs providing intermittent, episodic or limited drug delivery.An intermittent infusion pump is used to automatically administer adesired amount of liquid medicant to a patient. The liquid medicant issupplied from a reservoir and pumped into the patient via a catheter orother injection device. The manner in which the liquid is infused iscontrolled by the infusion pump controller, which may have various modesof infusion, such as a periodic release of medicine or a ramp mode inwhich the rate of infusion gradually increases, then remains constant,and then gradually decreases.

Additionally, many types of medications can be administered to a patientvia the respiratory tract. Delivery of drugs to the lungs by way ofinhalation is an important means of treating a variety of conditions,including such common local conditions as cystic fibrosis, pneumonia,bronchial asthma and chronic obstructive pulmonary disease and somesystemic conditions, including hormone replacement, pain management,immune deficiency, erythropoiesis, diabetes, etc. Steroids, betaagonists, anti-cholinergic agents, proteins and polypeptides are amongthe drugs that are administered to the lungs for such purposes. Suchdrugs are commonly administered to the lung in the form of an aerosol ofparticles of respirable size (less than about 10 μm in diameter). Theaerosol formulation can be presented as a liquid or a dry powder. Inorder to assure proper particle size in a liquid aerosol, particles canbe prepared in respirable size and then incorporated into a colloidialdispersion either containing a propellant as a metered dose inhaler(MDI) or air, such as in the case of a dry powder inhaler (DPI). For MDIapplication, an aerosol formulation is placed into an aerosol canisterequipped with a metered dose valve. In the hands of the patient theformulation is dispensed via an actuator adapted to direct the dose fromthe valve to the patient.

Delivery of medication via the respiratory tract may be preferred inmany circumstances because medication delivered this way enters thebloodstream very rapidly. Delivery of medication to the lungs may alsobe preferred when the medication is used in a treatment of a disease orcondition affecting the lungs in order to apply or target the medicationas close as physically possible to the diseased area.

Aerosol delivery of a medication to a patient's respiratory tract alsomay be performed while the patient is intubated, i.e. when anendotracheal tube is positioned in the patient's trachea to assist inbreathing. When an endotracheal tube is positioned in a patient, aproximal end of the endotracheal tube may be connected to a mechanicalventilator and the distal end is located in the trachea. An aerosol maybe added to the airflow in the ventilator circuit of the endotrachealtube and carried by the patient's inhalation to the lungs. A significantamount of the aerosolized medication may be deposited inside theendotracheal tube and the delivery rate of the medicine to the lungsalso remains relatively low and unpredictable.

Another use of an insufflator is to inflate a body cavity, like theabdominal cavity. Insufflation of the cavity is necessary to provide aworking space for a surgeon to examine the contents of the cavity oroperate within the cavity. Insufflating the abdominal cavity with gas,normally carbon dioxide, elevates the abdominal wall and pushes thecontents of the region, such as the bowel and the liver, away from theareas of the cavity requiring the surgeon's attention. Various gasinsufflators for use in the operating room are known. These insufflatorsinfuse between 4 and 6 liters of carbon dioxide into the abdomen,creating a distention pressure of 15 mmHg (0.33 psi).

The carbon dioxide for an operating room insufflation unit is suppliedby large pressurized tanks Flow rate and pressure may be regulated bycontrols located on the insufflator units, and monitors located on theunits display gas flow rate, gas pressure, and the total infusionvolume. For use in a doctor's office or emergency room, it is desirableto have a compact hand-held insufflation unit. Such a simplified unitwould provide an adequate volume of insufflation gas without the risk ofover insufflation.

In addition to delivering medication via gravity-fed intravenousinfusion, infusion pumps, inhalation, and insufflation, a drug may bedelivered subcutaneously by way of an aerosolized or atomizedmedicament. Generally, a physician may insert a delivery tube within anincision or body cavity of a patient to administer the drug to thesurface area of the body cavity.

As described above, there are a variety of means to administermedicaments to a patient. That is, therapeutic agents can be deliveredintravenously, subcutaneously, or respiratorily. However, thedistribution system of the present invention provides an apparatus andmethod of delivering pharmaceutical agents percutaneously to a desiredlocation while providing thorough dispersion of the medicament over alarge surface area.

FIG. 24 illustrates an exemplary embodiment of a drug distributionsystem 240 of the present invention. The system 240 includes an aerosolcanister 242 with a medicament, a control unit 244, and interconnectingtubing 246. The canister 242 may be pressurized with a gas/medicamentcombination. The gas may be carbon dioxide, nitrogen, oxygen, or otherbiocompatible gas. The medicament or agent may be a gas, liquid, power,solid, particulate, granule, crystal, or gel. An example of atherapeutic/pharmaceutical agent includes a hemostatic agent,antibiotic, bone morphogenic protein, chemotherapeutic agent, anestheticagent, agent that changes neovascularity, proteins, immunoglobulin,steroids, anti-inflammatory agent, angiogenesis factors, lidocaine,eqinephrine, ethrane, halofane, nitrous oxide, carbon dioxide, nitrogen,oxygen, opiates like OxyContin, morphine, Demerol, any agent describedherein, and combinations thereof

The control unit 244 may include a microprocessor and/or switches forcontrolling the release of the medicament. The microprocessor mayautomatically deliver the agent(s) within the body, while the switchesallow an operator to administer agent(s) manually. The control unit 244may control how the medicament is administered. That is, the medicamentmay be delivered in pulses, bursts, high pressure, low pressure, spray,stream, aerosolized, atomized, or combinations thereof. How themedicament is delivered determines the amount of tissue surface areathat is covered by the agent. For example, stream burst delivery wouldcover a small target site, while a spray burst aerosolized deliverywould cover a greater tissue area. The control unit may be remotecontrolled via a wire or RF, IR, optical, or microwave energy. Thecontrol unit may be operated by a physician, technician, and/or patient.The control unit may be time controlled for continuous or period drugdelivery.

The interconnecting tubing 246 of the drug delivery system may be madeof polymeric, metallic, composite, or ceramic material. The tubing 246may be biodegradable, biostable, and/or expandable. Multi-lumen tubingmay be used for delivery of two or more agents. The distal tip of thedelivery tube may include a needle (steerable or curved),omni-directional ports, and an atomizing/dispersing tip.

Referring now to FIG. 25, a multi-medicament delivery system 250 isshown. The system includes a gas container 252, a control unit 244, twoor more drug reservoirs 254, and connecting tubing 246. The container252 includes a gas with or without a medicament. The gas may be any ofthe gaseous substances disclosed herein. The control unit 244 mayinclude all or some of the characteristics of the control unit of FIG.25. The drug reservoirs 254 may be refillable and include any of thetherapeutic or pharmaceutical agents described herein. The tubingincludes a plurality of lumens 256 for delivery of the plurality ofagents.

Tissue Distraction

FIGS. 26 and 27 illustrate tissue distraction systems for use with thedrug delivery systems of the present invention. The distraction system260 of FIG. 26 includes a multi-channel catheter/cannula 262, anexpandable balloon 264, a balloon inflation tube 266, and a drugdelivery tube 268. In use, the system 260 is inserted in tissue adjacenta body region 272 which require the administration of one or moremedicaments. During insertion, the balloon 264 is deflated to minimizetissue displacement. Once positioned, the balloon 264 is inflated todistract tissue. The distal end of the drug delivery tube 268 ispositioned proximal from the balloon 264 such that medicament may beadministered to tissue located proximal to the balloon 264.

The distraction drug delivery system 270 of FIG. 27 is similar to thesystem of the FIG. 26 and includes similar structural features. In use,the system 270 is inserted in tissue adjacent a body region 272 whichrequires the administration of one or more medicaments. Duringinsertion, the balloon 264 is deflated to minimize tissue displacement.Once positioned, the balloon 264 is inflated to distract tissue. Thedistal end of the drug delivery tube 268 is positioned distal from theballoon 264 such that medicament may be administered to tissue locateddistal to the balloon 264. The systems 260/270 of FIGS. 26 and 27 allowtherapeutic and pharmaceutical agents to be delivered to a greatertissue surface area since the tissue is spaced apart by the inflatedballoon.

Dispersion

FIGS. 28A and 28B illustrate a drug dispersion member 280 foradministering one or more medicaments to the surface of tissue. Thedispersion member 280 includes porous material 284 for allowingmedicaments to flow therethrough. The member 280 may be made of foam,fabric, polymer, metal, ceramic, composite, or combinations thereof. Itmay be biodegradable or biostable. The dispersion member 280 may includea channel 286 dimensioned for receiving a delivery tube 288 of a drugdelivery system previously described. In FIG. 28B, the member 280 isimplanted in tissue 282 such that the outer surface of the membercontacts the tissue surface. The delivery tube 288 is inserted in thechannel 286 of the member 280. The tube 288 may includemicroenvironment-controlling devices, such as sensors 14, magnets 102,heating/cooling units 18, drug ports 16, and pressure ports 16. With thetube positioned, one or more medicaments may be expelled from the tube288 and captured by the porous material 284 of the disbursement member280. The member and its pores function as a wick to carry the agent(s)to the adjacent tissue. The microenvironment of the adjacent tissue maybe measured, changed, and monitored by the dispersion member.

Internal Aerosol Delivery

The embodiments shown in FIGS. 24 and 25 were configured for externaldrug administration. However, in FIGS. 29A and 29B, implantable deliverysystems are illustrated. The implantable systems include similarstructural elements as the systems of FIGS. 24 and 25. In FIG. 29A, thecontrol unit/reservoir 38/42, microenvironment-controlling devices, andtubing are implanted in the patient 294. A refill port 292 is positionedin the skin and is connected to the internal tubing. The medicament/gascanister 298 is connected to the refill port 292 for recharging theinternal reservoir 40. The embodiment of FIG. 29B is completelyimplanted. The canister 298 along with the other components ispositioned in the patient. The control unit 38 of the system may beoperated with a remote 296 via RF, IR, optical, or microwave energy. Themicroenvironment of internal body tissue may be measured, changed, andmonitored by the implantable delivery systems.

Generator Joint

In a related invention, a generator joint 300 is illustrated in FIGS.30A and 30B. A replacement component or total joint replacement implant302 may include magnets 304 and winding 306 for generating electricalcurrent. The joint may be the knee, shoulder, hip, spine, elbow, wrist,ankle, or a joint of the foot or hand. The electrical current may beused to power any of the microenvironment-controlling systems describedherein or to power any other implant. In an exemplary embodiment, atotal knee replacement implant 302 is shown. The implant componentsinclude magnets 304, windings 306, and electrical wires. As the knee ismoved or rotated naturally, the relative movement of the magnets andwindings create an electrical current. This current may be utilized topower sensors, heating/cooling units, electromagnets, drug pumps, or anyother microenvironment-controlling device.

Fuel Cell

In a further related invention, a fuel cell may be used to power themicroenvironment-controlling apparatus of the present invention. Fuelcells generate electricity by combining hydrogen with oxygen. In anexemplary embodiment, the fuel cell runs on alcohol such as methanol.The power source for the devices of the present invention may also be ahybrid of battery power and a fuel cell.

Heat Probe

FIGS. 31 and 32 depict a needle shaped device 400,402 for microclimateheating in the body. Wires 404,406 convey electrical energy to a heaterat the needle tip. In needle 402, a single wire 410 provides power incombination with a chassis ground 412, enabling the needle to have amore narrow diameter. Needles 400,402 may be combined with systemsdescribed herein, where it is advantageous to control temperature. Wires404,406, and 410 are controllable by a system microcontroller, asdescribed above.

Magnetic Heating

FIGS. 33 and 34 illustrate a method of heating magnetic materialimplanted proximate the site for which microclimate control is desired.FIG. 3 illustrates a sinusoidal waveform representative of the change inmagnetic pull. By rapidly changing the poles, indicate as N north and Ssouth, magnetic particles within the body are excited and thus generateheat. Circuit 414 is illustrative of a means for such rapid polarchanging, under microprocessor 416 control. As can be seen in FIG. 35, acircuit 415 may be used to precisely monitor the temperature generated,incorporating thermocouple 418.

It may be advantageous to coordinate or correlate magnetic pulses withthe heart rate, for improved efficacy of a therapeutic substancedelivered as described above. With reference to FIG. 36, a circuit 440is shown, with a heart rate monitor 442, magnetic field output 444,microprocessor 446, real time clock 448 for microprocessor control andpower saving, and a serial interface 450 for downloading a deliveryprofile. FIG. 37 illustrates a corresponding signal profile, with trace460 indicating the heart beat, and trace 462 indicating the programmeddelivery profile correlated therewith.

Energy Delivery

With reference to FIG. 38, a circuit 470 is illustrated, operative totransmit radio frequency (RF) energy. Illustrated are frequencygenerator 472, pre-amplifier 474, frequency multiplier 476, poweramplifiers 480, and output antenna 482. In this application, an implant(not shown) has an antenna that would receive the energy transmitted at482 to power the implant, and or to directly warm the tissue proximatethe implant.

FIG. 39 illustrates and ultrasonic generator circuit having componentsanalogous to FIG. 38, with the inclusion of a feedback loop 492operative to create a phase lock loop signal. Feedback mechanisms may bebased on constant phase, mm impedance or other methods.

FIG. 40 illustrates a resistive heater circuit 500 including amicroprocessor/microcontroller 502 and heating element 504.

It is contemplated the microenvironment-controlling systems of thepresent invention may be used with and integrated with the methods anddevices disclosed in U.S. Provisional Application No. 60/765,857entitled “Surgical Fixation Device” filed on Feb. 7, 2006. In the '857document, various thermoplastic fixation devices are disclosed. Thefixation devices may be, but are not limited to, degradable,biodegradable, bioerodible, bioabsorbable, mechanically expandable,hydrophilic, bendable, deformable, malleable, riveting, threaded,toggling, barded, bubbled, laminated, coated, blocking, pneumatic,one-piece, multi-component, solid, hollow, polygon-shaped, pointed,self-introducing, and combinations thereof. Also, the devices mayinclude, but are not limited to, metallic material, polymeric material,ceramic material, composite material, body tissue, synthetic tissue,hydrophilic material, expandable material, compressible material, heatbondable material, and combinations thereof.

The methods and devices disclosed in the '857 document may be used inconjunction with any surgical procedure of the body. The fastening andrepair of tissue or an implant may be performed in connection withsurgery of a joint, bone, muscle, ligament, tendon, cartilage, capsule,organ, skin, nerve, vessel, or other body parts. For example, tissue maybe repaired during intervertebral disc surgery, knee surgery, hipsurgery, organ transplant surgery, bariatric surgery, spinal surgery,anterior cruciate ligament (ACL) surgery, tendon-ligament surgery,rotator cuff surgery, capsule repair surgery, fractured bone surgery,pelvic fracture surgery, avulsion fragment surgery, shoulder surgery,hernia repair surgery, and surgery of an intrasubstance ligament tear,annulus fibrosis, fascia lata, flexor tendons, etc.

It is contemplated that the devices and methods of the present inventionbe applied using minimally invasive incisions and techniques to fastenmuscles, tendons, ligaments, bones, nerves, and blood vessels. A smallincision(s) may be made adjacent the damaged tissue area to be repaired,and a tube, delivery catheter, sheath, cannula, or expandable cannulamay be used to perform the methods of the present invention. U.S. Pat.No. 5,320,611 entitled “Expandable Cannula Having Longitudinal Wire andMethod of Use” discloses cannulas for surgical and medical useexpandable along their entire lengths. The cannulas are inserted throughtissue when in an unexpanded condition and with a small diameter. Thecannulas are then expanded radially outwardly to give a full-sizeinstrument passage. Expansion of the cannulas occurs against theviscoelastic resistance of the surrounding tissue. The expandablecannulas do not require a full depth incision, or at most require only aneedle-size entrance opening.

U.S. Pat. Nos. 5,674,240; 5,961,499; and 6,338,730 also disclosecannulas for surgical and medical use expandable along their lengths.The cannula can be provided with a pointed end portion and can includewires having cores which are enclosed by jackets. The jackets areintegrally formed as one piece with a sheath of the cannula. The cannulamay be expanded by inserting members or by fluid pressure. An expandablechamber may be provided at the distal end of the cannula. The abovementioned patents are hereby incorporated by reference.

In addition to using a cannula with the present invention, an introducermay be utilized to position implants at a specific location within thebody. U.S. Pat. No. 5,948,002 entitled “Apparatus and Method for Use inPositioning a Suture Anchor” discloses devices for controlling theplacement depth of a fastener. Also, U.S. patent application Ser. No.10/102,413 discloses methods of securing body tissue with a roboticmechanism. The above-mentioned patent and application are herebyincorporated by reference. Another introducer or cannula which may beused with the present invention is the VersaStep® System by Tyco®Healthcare.

The present invention may also be utilized with minimally invasivesurgery techniques disclosed in U.S. Pat. Nos. 6,702,821; 6,770,078; and7,104,996. These patent documents disclose, inter alia, apparatus andmethods for minimally invasive joint replacement. The femoral, tibial,and/or patellar components of a knee replacement may be fastened orlocked to each other and to adjacent tissue using fixation devicesdisclosed herein and incorporated by reference. Furthermore, the methodsand devices of the present invention may be utilized for repairing,reconstructing, augmenting, and securing tissue or implants during and“on the way out” of a knee replacement procedure. For example, theanterior cruciate ligament and other ligaments may be repaired orreconstructed; quadriceps mechanisms and other muscles may be repaired;a damaged rotator cuff may be mended. The patent documents mentionedabove are hereby incorporated by reference.

It is further contemplated that the present invention may be used inconjunction with the devices and methods disclosed in U.S. Pat. No.5,329,846 entitled “Tissue Press and System” and U.S. Pat. No. 5,269,785entitled “Apparatus and Method for Tissue Removal.” For example, animplant of the present invention may include tissue harvested,configured, and implanted as described in the patents. Theabove-mentioned patents are hereby incorporated by reference.

Additionally, it is contemplated that the devices and methods of thepresent invention may be used with heat bondable materials as disclosedin U.S. Pat. No. 5,593,425 entitled “Surgical Devices Assembled UsingHeat Bondable Materials.” For example, the implants of the presentinvention may include thermoplastic material. The material may bedeformed to secure tissue or hold a suture or cable. The fasteners madeof heat bondable material may be mechanically crimped, plasticallycrimped, or may be welded to a suture or cable with RF (Bovie devices),laser, ultrasound, electromagnet, ultraviolet, infrared,electro-shockwave, or other known energy. The welding may be performedin an aqueous, dry, or moist environment. The welding device may bedisposable, sterilizable, single-use, and/or battery-operated. Theabove-mentioned patent is hereby incorporated by reference.

Furthermore, the methods of the present invention may be performed underindirect visualization, such as endoscopic guidance, computer assistednavigation, magnetic resonance imaging, CT scan, ultrasound,fluoroscopy, X-ray, or other suitable visualization technique. Theimplants of the present invention may include a radiopaque material forenhancing indirect visualization. The use of these visualization meansalong with minimally invasive surgery techniques permits physicians toaccurately and rapidly repair, reconstruct, augment, and secure tissueor an implant within the body. U.S. Pat. Nos. 5,329,924; 5,349,956; and5,542,423 disclose apparatus and methods for use in medical imaging.Also, the present invention may be performed using robotics, such ashaptic arms or similar apparatus. The above-mentioned patents are herebyincorporated by reference.

All references cited herein are expressly incorporated by reference intheir entirety.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed herein above. In addition, unless mention was made above tothe contrary, it should be noted that all of the accompanying drawingsare not to scale. A variety of modifications and variations are possiblein light of the above teachings without departing from the scope andspirit of the invention.

1-19. (canceled)
 20. A system for controlling an environment of apatient undergoing a surgical procedure, said system comprising: aconduit configured to direct a fluid stream toward the environment; asensor configured to measure at least one parameter of one of theenvironment; an effector comprising a reservoir operatively connected tothe conduit and containing an agent in selective communication with theconduit, wherein the agent is configured to change the at least oneparameter of the environment; and a controller configured to selectivelyactivate the effector based on a signal received from the sensor todeliver the agent into the conduit.
 21. A system as set forth in claim20, wherein the agent is a fluid agent.
 22. A system as set forth inclaim 21, wherein the controller comprises a reservoir controllerconfigured to selectively release the fluid agent into the conduit tochange the parameter of the environment.
 23. A system as set forth inclaim 22, wherein the fluid agent is fluidly separated from the conduituntil the reservoir controller releases the fluid agent into theconduit.
 24. A system as set forth in claim 20, wherein the sensorcomprises a pH sensor.
 25. A system as set forth in claim 24, whereinthe fluid agent comprises a pH controlling substance, whereby release ofthe agent into the conduit adjusts a pH of the fluid stream.
 26. Asystem as set forth in claim 25, wherein the pH controlling substance isconfigured to make the fluid stream more basic.
 27. A system as setforth in claim 26, wherein the pH controlling substance comprises acalcium-based substance.
 28. A system as set forth in claim 26, whereinthe pH controlling substance comprises at least one of sodium chloride,potassium chloride, calcium carbonate, and calcium sulfate.
 29. A systemas set forth in claim 25, wherein the pH controlling substance isconfigured to make the fluid stream more acidic.
 30. A system as setforth in claim 29, wherein the pH controlling substance comprises carbondioxide.
 31. A system as set forth in claim 20, further comprisingtemperature effector, a temperature sensor, and a temperaturecontroller.
 32. A method of controlling an environment of a patientundergoing a surgical procedure, said method comprising: positioning aconduit to direct a fluid stream toward the environment; directing thefluid stream through the conduit toward the environment; sensing atleast one parameter of the environment with a sensor; receiving a sensorsignal from the sensor with a controller, the sensor signal beingindicative of the at least one parameter of the environment; sending acontrol signal from the controller to an effector operatively connectedto the conduit based on the received sensor signal; and activating, inresponse to the control signal, the effector to deliver an agent from areservoir of the effector into the conduit to change the parameter ofthe environment.
 33. A method as set forth in claim 32, wherein thesensor comprises a pH sensor, and the agent adjusts the pH of the fluidstream.